FX-6000T细胞牵张 FX-6000 Tension System细胞牵张拉伸系统

flexcell品牌FX-6000T细胞牵张拉伸应力加载系统(Flexcell FX6000 Tension system)

2D/3D细胞或组织静态或动态牵张等边轴或单轴向牵张应变加载和实时观察
新增不用基底硬度牵张

亮点：

适用样品：细胞或者组织（2D、3D）
轴向：二维等边轴、二维单轴向、三维等边轴、三维单轴向、三维梯形牵张
牵张模式：真空动力抻拉培养板弹性柔性基底膜或3D水凝胶包埋的细胞
实时观察：StageFlexer显微附属设备可在显微镜下观察牵张作用下反应
方便对照：可控制同一块培养板部分孔细胞受力与否
多组牵张条件作用对照：可同时运行多个不同压力大小、不同频率
不同加载周期程序，方便多组牵张条件对比；
软件精准调控：对牵张加载周期、张应变大小、频率、波形智能调控
牵张范围：0 - 33%
牵张频率：0.01- 5 Hz
细胞量大，便于后期分析：系统牵张传导仪支持4块6孔
（每孔1.2* 105个细胞）或24孔牵张板，可同时兼容4个独立
的FlexLink牵张加载传导仪 ，独立操作四个不同的实验程序
支持任何波形种类：如更好地控制在超低或超高应力下形：

细胞牵张受力同时可在倒置、正置显微镜下实时观察细胞受力变化和反应。

CellSoft不同硬度基底培养板可以在弹性模量范围1-80kPa范围内牵张

典型应用:

该系统感应各种细胞在应力刺激下的生物化学反应，例如：骨骼细胞，肺细胞，心肌细胞，血细胞，皮肤细胞，
肌腱细胞，韧带细胞，软骨细胞和骨细胞等各种2D或3D细胞组织。
典型应用科室:

CellSoft™ 培养板

•弹性模量范围1-80kPa

•可选多孔板、60mm和100mm培养板

•BioFlex® CellSoft™ 标准6孔板

•在柔性基底上牵拉细胞

•腔室载玻片CellSoft™

•表面蛋白包被，无菌单独包装

CellSoft™ 培养板有很多不同的种类，如不同的硬度，不同的孔板，用于显微观察的腔室载玻片（圆形多孔板），共价包被Collagen I或其他蛋白，可对细胞进行静态或动态牵拉应力刺激。更重要的一点，新型的CellSoft™ 培养板可以反复胰酶消化和再接种细胞，蛋白包被的表面可以重复使用多达三次。

CellSoft不同硬度基底牵张文献：

Key References:

Buxboim et al., How deeply do cells feel:methods for thin gels. J Phys Condens matter. 22: 1-19, 2010.

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Chodhury et al., Soft substrates promote homogeneous self-renewal of embryonic stem cells via down regulating cell-matrix tractions. PLOS 1 5: 1-10, 2010.

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Engle et al., Matrix elasticity directs stem cell lineage specification. Cell 126: 677-689, 2006.

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Hirata and Yamaoka. Effect of stem cell niche elasticity/ECM protein on the self-beating cardiomyocyte differentiation of iPS cells at different stages. Acta Biomat. 65: 44-52, 2018

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Megone et al., Impact of surface adhesion and sample heterogeneity on the multiscale mechanical characterization of soft biomaterials. Sci Rep 8: 6780, 2018.

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Ou et al., Visualizing mechanical modulation of nanoscale organization of cell-matrix adhesions. Integr. Biol. 8: 795-804,2016.

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Palchesko et al., Development of polydimethylsiloxane substrates with tunable elastic modulus to study cell mechanobiology in muscle and nerve. PLOS 1 7: 1-13, 2012

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Smith et al., Mechanosensing of matrix by stem cells: from matrix heterogeneity, contractility and the nucleus in pore-migration to cardiogenesis and muscle stem cells in vivo. Sem Cell Devtbio. 71: 84-98, 2017

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Solon et al., Fibroblast adaptation andstiffness matching to soft elastic substrates. Biophys J. 93: 4453-4461, 2007.

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Thomas et al., Measuring the mechanical properties of living cells using atomic force microscopy. J Visual Exp. 76:1-8, 2013.

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Vertelov et al., Rigidity of silicone substrates controls cell spreading and stem cell differentiation. Sci Rep. 6:1-10, 2016.

flexcell tension system应用文献：

BLADDER
BLADDER SMOOTH MUSCLE CELLS
1. Adam RM, Eaton SH, Estrada C, Nimgaonkar A, Shih SC, Smith LE, Kohane IS, Bagli D, Freeman MR. Mechanical stretch is a highly selective regulator of gene expression in human bladder smooth muscle cells. Physiol Genomics 20(1):36-44, 2004.
2. Adam RM, Roth JA, Cheng HL, Rice DC, Khoury J, Bauer SB, Peters CA, Freeman MR. Signaling through PI3K/Akt mediates stretch and PDGF-BB-dependent DNA synthesis in bladder smooth muscle cells. J Urol 169(6):2388-2393, 2003.
3. Aitken KJ, Block G, Lorenzo A, Herz D, Sabha N, Dessouki O, Fung F, Szybowska M, Craig L, Bagli DJ. Mechanotransduction of extracellular signal-regulated kinases 1 and 2 mitogen-activated protein kinase activity in smooth muscle is dependent on the extracellular matrix and regulated by matrix metalloproteinases. Am J Pathol 169(2):459-470, 2006.
4. Aitken KJ, Tolg C, Panchal T, Leslie B, Yu J, Elkelini M, Sabha N, Tse DJ, Lorenzo AJ, Hassouna M, Bägli DJ. Mammalian target of rapamycin (mTOR) induces proliferation and de-differentiation responses to three coordinate pathophysiologic stimuli (mechanical strain, hypoxia, and extracellular matrix remodeling) in rat bladder smooth muscle. Am J Pathol 176(1):304-319, 2010.
5. Chaqour B, Yang R, Sha Q. Mechanical stretch modulates the promoter activity of the profibrotic factor CCN2 through increased actin polymerization and NF-B activation. J Biol Chem 281(29):20608-20622, 2006.
6. Estrada CR, Adam RM, Eaton SH, Bägli DJ, Freeman MR. Inhibition of EGFR signaling abrogates smooth muscle proliferation resulting from sustained distension of the urinary bladder. Lab Invest 86(12):1293-1302, 2006.
7. Galvin DJ, Watson RW, Gillespie JI, Brady H, Fitzpatrick JM. Mechanical stretch regulates cell survival in human bladder smooth muscle cells in vitro. Am J Physiol Renal Physiol 283(6):F1192-F1199, 2002.
8. Halachmi S, Aitken KJ, Szybowska M, Sabha N, Dessouki S, Lorenzo A, Tse D, Bagli DJ. Role of signal transducer and activator of transcription 3 (STAT3) in stretch injury to bladder smooth muscle cells. Cell Tissue Res 326(1):149-158, 2006.
9. Hubschmid U, Leong-Morgenthaler PM, Basset-Dardare A, Ruault S, Frey P. In vitro growth of human urinary tract smooth muscle cells on laminin and collagen type I-coated membranes under static and dynamic conditions. Tissue Engineering 11(1-2):161-171, 2005.
10. Kushida N, Kabuyama Y, Yamaguchi O, Homma Y. Essential role for extracellular Ca2+ in JNK activation by mechanical stretch in bladder smooth muscle cells. Am J Physiol Cell Physiol 281(4):C1165-C1172, 2001.
11. Nguyen HT, Adam RM, Bride SH, Park JM, Peters CA, Freeman MR. Cyclic stretch activates p38 SAPK2-, ErbB2-, and AT1-dependent signaling in bladder smooth muscle cells. Am J Physiol Cell Physiol 279(4):C1155-C1167, 2000.
12. Orsola A, Adam RM, Peters CA, Freeman MR. The decision to undergo DNA or protein synthesis is determined by the degree of mechanical deformation in human bladder muscle cells. Urology 59(5):779-783, 2002.
13. Orsola A, Estrada CR, Nguyen HT, Retik AB, Freeman MR, Peters CA, Adam RM. Growth and stretch response of human exstrophy bladder smooth muscle cells: molecular evidence of normal intrinsic function. BJU Int 95(1):144-148, 2005.
14. Park JM, Adam RM, Peters CA, Guthrie PD, Sun Z, Klagsbrun M, Freeman MR. AP-1 mediates stretch-induced expression of HB-EGF in bladder smooth muscle cells. Am J Physiol Cell Physiol 277:C294-C301, 1999.
15. Park JM, Borer JG, Freeman MR, Peters CA. Stretch activates heparin-binding EGF-like growth factor expression in bladder smooth muscle cells. Am J Physiol Cell Physiol 275:C1247-C1254, 1998.
16. Park JM, Yang T, Arend LJ, Schnermann JB, Peters CA, Freeman MR, Briggs JP. Obstruction stimulates COX-2 expression in bladder smooth muscle cells via increased mechanical stretch. Am J Physiol Renal Physiol 276:F129-F136, 1999.
17. Persson K, Sando JJ, Tuttle JB, Steers WD. Protein kinase C in cyclic stretch-induced nerve growth factor production by urinary tract smooth muscle cells. Am J Physiol Cell Physiol 269:C1018-C1024, 1995.
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18. Steers WD, Broder SR, Persson K, Bruns DE, Ferguson JE 2nd, Bruns ME, Tuttle JB. Mechanical stretch increases secretion of parathyroid hormone-related protein by cultured bladder smooth muscle cells. J Urol 160(3 Pt 1):908-912, 1998.
19. Upadhyay J, Aitken KJ, Damdar C, Bolduc S, Bagli DJ. Integrins expressed with bladder extracellular matrix after stretch injury in vivo mediate bladder smooth muscle cell growth in vitro. J Urol 169(2):750-755, 2003.
20. Wang Y, Xiong Z, Gong W, Zhou P, Xie Q, Zhou Z, Lu G. Expression of heat shock protein 27 correlates with actin cytoskeletal dynamics and contractility of cultured human bladder smooth muscle cells. Exp Cell Res 338(1):39-44, 2015.
21. Yang R, Amir J, Liu H, Chaqour B. Mechanical strain activates a program of genes functionally involved in paracrine signaling of angiogenesis. Physiol Genomics 36(1):1-14, 2008.
22. Yu G, Bo S, Xiyu J, Enqing X. Effect of bladder outlet obstruction on detrusor smooth muscle cell: an in vitro study. Journal of Surgical Research 114(2):202-209, 2003.
23. Zhou D, Herrick DJ, Rosenbloom J, Chaqour B. Cyr61 mediates the expression of VEGF, v-integrin, and -actin genes through cytoskeletally based mechanotransduction mechanisms in bladder smooth muscle cells. J Appl Physiol 98(6):2344-2354, 2005.
UROTHELIAL & UROEPITHELIAL CELLS
24. Jerde TJ, Mellon WS, Bjorling DE, Nakada SY. Evaluation of urothelial stretch-induced cyclooxygenase-2 expression in novel human cell culture and porcine in vivo ureteral obstruction models. J Pharmacol Exp Ther 317(3):965-972, 2006.
25. Jerde TJ, Mellon WS, Bjorling DE, Checura CM, Owusu-Ofori K, Parrish JJ, Nakada SY. Stretch induction of cyclooxygenase-2 expression in human urothelial cells is calcium- and protein kinase C -dependent. Mol Pharmacol 73(1):18-26, 2008. Erratum in: Mol Pharmacol 74(2):539, 2008.
26. Sun Y, Chai TC. Effects of dimethyl sulphoxide and heparin on stretch-activated ATP release by bladder urothelial cells from patients with interstitial cystitis. BJU Int 90(4):381-385, 2002.
27. Sun Y, Chai TC. Up-regulation of P2X3 receptor during stretch of bladder urothelial cells from patients with interstitial cystitis. J Urol 171(1):448-452, 2004.
28. Sun Y, Keay S, De Deyne PG, Chai TC. Augmented stretch activated adenosine triphosphate release from bladder uroepithelial cells in patients with interstitial cystitis. Journal of Urology 166(5):1951-1956, 2001.
29. Sun Y, Keay S, DeDeyne P, Chai T. Stretch-activated release of adenosine triphosphate by bladder uroepithelia is augmented in interstitial cystitis [abstract]. Urology 57(6 Suppl 1):131, 2001.
30. Sun Y, MaLossi J, Jacobs SC, Chai TC. Effect of doxazosin on stretch-activated adenosine triphosphate release in bladder urothelial cells from patients with benign prostatic hyperplasia. Urology 60(2):351-356, 2002.
BONE
1. Acosta FL, Pham M, Safai Y, Buser Z. Improving bone formation in osteoporosis through in vitro mechanical stimulation compared to biochemical stimuli. Journal of Nature and Science 1(4):e63, 2015.
2. Aguirre JI, Plotkin LI, Gortazar AR, Millan MM, O'Brien CA, Manolagas SC, Bellido T. A novel ligand-independent function of the estrogen receptor is essential for osteocyte and osteoblast mechanotransduction. J Biol Chem 282(35):25501–25508, 2007.
3. Bellido T, Plotkin LI. Detection of apoptosis of bone cells in vitro. Methods in Molecular Biology, Vol. 455: Osteoporosis: Methods and Protocols. Edited by Westendorf JJ. Humana Press: Totowa, 51-75, 2008.
4. Bhatt KA, Chang EI, Warren SM, Lin SE, Bastidas N, Ghali S, Thibboneir A, Capla JM, McCarthy JG, Gurtner GC. Uniaxial mechanical strain: an in vitro correlate to distraction osteogenesis. J Surg Res 143(2):329-36, 2007.
5. Boutahar N, Guignandon A, Vico L, Lafage-Proust MH. Mechanical strain on osteoblasts activates autophosphorylation of focal adhesion kinase and proline-rich tyrosine kinase 2 tyrosine sites involved in ERK activation. J Biol Chem 279(29):30588-30599, 2004.
6. Buckley MJ, Banes AJ, Jordan RD. The effects of mechanical strain on osteoblasts in vitro. J Oral Maxillofac Surg 48(3):276-282, 1990.
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7. Buckley MJ, Banes AJ, Levin LG, Sumpio BE, Sato M, Jordan R, Gilbert J, Link GW, Tran Son Tay R. Osteoblasts increase their rate of division and align in response to cyclic, mechanical tension in vitro. Bone Miner 4(3):225-236, 1988.
8. Calvalho RS, Bumann A, Schwarzer C, Scott E, Yen EH. A molecular mechanism of integrin regulation from bone cells stimulated by orthodontic forces. Eur J Orthod 18(3):227-235, 1996.
9. Carvalho RS, Scott JE, Suga DM, Yen EH. Stimulation of signal transduction pathways in osteoblasts by mechanical strain potentiated by parathyroid hormone. J Bone Miner Res 9(7):999-1011, 1994.
10. Carvalho RS, Scott JE, Yen EH. The effects of mechanical stimulation on the distribution of 1 integrin and expression of 1-integrin mRNA in TE-85 human osteosarcoma cells. Arch Oral Biol 40(3):257-264, 1995.
11. Case N, Ma M, Sen B, Xie Z, Gross TS, Rubin J. -catenin levels influence rapid mechanical responses in osteoblasts. J Biol Chem 283(43):29196-29205, 2008.
12. Chen X, Macica CM, Ng KW, Broadus AE. Stretch-induced PTH-related protein gene expression in osteoblasts. J Bone Miner Res 20(8):1454-61, 2005.
13. Chen YJ, Chang MC, Yao CC, Lai HH, Chang J, Jeng JH. Mechanoregulation of osteoblast-like MG-63 cell activities by cyclic stretching. J Formos Med Assoc 113(7):447-53, 2014.
14. Chung E, Sampson AC, Rylander MN. Influence of heating and cyclic tension on the induction of heat shock proteins and bone-related proteins by MC3T3-E1 cells. Biomed Res Int 2014:354260, 2014.
15. Cillo JE Jr, Gassner R, Koepsel RR, Buckley MJ. Growth factor and cytokine gene expression in mechanically strained human osteoblast-like cells: implications for distraction osteogenesis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 90(2):147-154, 2000.
16. Delaine-Smith RM, Javaheri B, Helen Edwards J, Vazquez M, Rumney RM. Preclinical models for in vitro mechanical loading of bone-derived cells. Bonekey Rep 4:728, 2015.
17. Duncan RL, Hruska KA. Chronic, intermittent loading alters mechanosensitive channel characteristics in osteoblast-like cells. Am J Physiol Renal Physiol 267:F909-F916, 1994.
18. Fan X, Rahnert JA, Murphy TC, Nanes MS, Greenfield EM, Rubin J. Response to mechanical strain in an immortalized pre-osteoblast cell is dependent on ERK1/2. J Cell Physiol 207(2):454-460, 2006.
19. Faure C, Linossier MT, Malaval L, Lafage-Proust MH, Peyroche S, Vico L, Guignandon A. Mechanical signals modulated vascular endothelial growth factor-A (VEGF-A) alternative splicing in osteoblastic cells through actin polymerisation. Bone 42(6):1092-1101, 2008.
20. Faure C, Vico L, Tracqui P, Laroche N, Vanden-Bossche A, Linossier MT, Rattner A, Guignandon A. Functionalization of matrices by cyclically stretched osteoblasts through matrix targeting of VEGF. Biomaterials 31(25):6477-6484, 2010.
21. Gao J, Fu S, Zeng Z, Li F, Niu Q, Jing D, Feng X. Cyclic stretch promotes osteogenesis-related gene expression in osteoblast-like cells through a cofilin-associated mechanism. Mol Med Rep 14(1):218-24, 2016.
22. Geng WD, Boskovic G, Fultz ME, Li C, Niles RM, Ohno S, Wright GL. Regulation of expression and activity of four PKC isozymes in confluent and mechanically stimulated UMR-108 osteoblastic cells. J Cell Physiol 189(2):216-228, 2001.
23. Gortazar AR, Martin-Millan M, Bravo B, Plotkin LI, Bellido T. Crosstalk between caveolin-1/extracellular signal-regulated kinase (ERK) and β-catenin survival pathways in osteocyte mechanotransduction. J Biol Chem 288(12):8168-8175, 2013.
24. Granet C, Boutahar N, Vico L, Alexandre C, Lafage-Proust MH. MAPK and SRC-kinases control EGR-1 and NF-B inductions by changes in mechanical environment in osteoblasts. Biochem Biophys Res Commun 284(3):622-631, 2001.
25. Granet C, Vico AG, Alexandre C, Lafage-Proust MH. MAP and src kinases control the induction of AP-1 members in response to changes in mechanical environment in osteoblastic cells. Cellular Signaling 14(8):679-688, 2002.
26. Grimston SK, Screen J, Haskell JH, Chung DJ, Brodt MD, Silva MJ, Civitelli R. Role of connexin43 in osteoblast response to physical load. Ann N Y Acad Sci 1068:214-224, 2006.
27. Guignandon A, Akhouayri O, Usson Y, Rattner A, Laroche N, Lafage-Proust MH, Alexandre C, Vico L. Focal contact clustering in osteoblastic cells under mechanical stresses: microgravity and cyclic deformation. Cell Commun Adhes 10(2):69-83, 2003.
28. Guignandon A, Boutahar N, Rattner A, Vico L, Lafage-Proust MH. Cyclic strain promotes shuttling of PYK2/Hic-5 complex from focal contacts in osteoblast-like cells. Biochem Biophys Res Commun 343(2):407-14, 2006.
29. Han L, Zhang X, Tang G. Indian Hedgehog signaling is involved in the stretch induced proliferation of osteoblast. Hua Xi Kou Qiang Yi Xue Za Zhi 30(3):234-8, 2012.
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30. Hara F, Fukuda K, Asada S, Matsukawa M, Hamanishi C. Cyclic tensile stretch inhibition of nitric oxide release from osteoblast-like cells is both G protein and actin-dependent. Journal of Orthopaedic Research 19(1):126-131, 2001.
31. Hara F, Fukuda K, Ueno M, Hamanishi C, Tanaka S. Pertussis toxin-sensitive G proteins as mediators of stretch-induced decrease in nitric-oxide release of osteoblast-like cells. J Orthop Res 17(4):593-597, 1999.
32. Hens JR, Wilson KM, Dann P, Chen X, Horowitz MC, Wysolmerski JJ. TOPGAL mice show that the canonical Wnt signaling pathway is active during bone development and growth and is activated by mechanical loading in vitro. J Bone Miner Res 20(7):1103-1113, 2005.
33. Ho AM, Marker PC, Peng H, Quintero AJ, Kingsley DM, Huard J. Dominant negative Bmp5 mutation reveals key role of BMPs in skeletal response to mechanical stimulation. BMC Dev Biol 8:35, 2008.
34. Jansen JH, Weyts FA, Westbroek I, Jahr H, Chiba H, Pols HA, Verhaar JA, van Leeuwen JP, Weinans H. Stretch-induced phosphorylation of ERK1/2 depends on differentiation stage of osteoblasts. Journal of Cellular Biochemistry 93:542–551, 2004.
35. Kameyama S, Yoshimura Y, Kameyama T, Kikuiri T, Matsuno M, Deyama Y, Suzuki K, Iida J. Short-term mechanical stress inhibits osteoclastogenesis via suppression of DC-STAMP in RAW264.7 cells. Int J Mol Med 31(2):292-8, 2013.
36. Kao CT, Chen CC, Cheong UI, Liu SL, Huang TH. Osteogenic gene expression of murine osteoblastic (MC3T3-E1) cells under cyclic tension. Laser Phys 24:8, 085605, 2014.
37. Karasawa Y, Tanaka H, Nakai K, Tanabe N, Kawato T, Maeno M, Shimizu N. Tension force downregulates matrix metalloproteinase expression and upregulates the expression of their inhibitors through MAPK signaling pathways in MC3T3-E1 cells. Int J Med Sci 12(11):905-13, 2015.
38. Kariya T, Tanabe N, Shionome C, Kawato T, Zhao N, Maeno M, Suzuki N, Shimizu N. Tension force-induced ATP promotes osteogenesis through P2X7 receptor in osteoblasts. J Cell Biochem 116(1):12-21, 2015.
39. Kim DW, Lee HJ, Karmin JA, Lee SE, Chang SS, Tolchin B, Lin S, Cho SK, Kwon A, Ahn JM, Lee FY. Mechanical loading differentially regulates membrane-bound and soluble RANKL availability in MC3T3-E1 cells. Ann N Y Acad Sci 1068:568-72, 2006.
40. Knoll B, McCarthy TL, Centrella M, Shin J. Strain-dependent control of transforming growth factor- function in osteoblasts in an in vitro model: biochemical events associated with distraction osteogenesis. Plastic & Reconstructive Surgery 116(1):224-233, 2005.
41. Li L, Chen M, Deng L, Mao Y, Wu W, Chang M, Chen H. The effect of mechanical stimulation on the expression of 2, 1, 3 integrins and the proliferation, synthetic function in rat osteoblasts. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 20(2):187-192, 2003.
42. Li L, Deng L, Chen M, Wu W, Mao Y, Chen H. The effect of mechanical stimulation on the proliferation and synthetic function of osteoblasts from osteoporotic rat. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 21(3):341-346, 349, 2004.
43. Li X, Zhang XL, Shen G, Tang GH. Effects of tensile forces on serum deprivation-induced osteoblast apoptosis: expression analysis of caspases, Bcl-2, and Bax. Chin Med J (Engl) 125(14):2568-2573, 2012.
44. Li Y, Tang L, Duan Y, Ding Y. Upregulation of MMP-13 and TIMP-1 expression in response to mechanical strain in MC3T3-E1 osteoblastic cells. BMC Res Notes 3:309, 2010.
45. Liegibel UM, Sommer U, Tomakidi P, Hilscher U, Van Den Heuvel L, Pirzer R, Hillmeier J, Nawroth P, Kasperk C. Concerted action of androgens and mechanical strain shifts bone metabolism from high turnover into an osteoanabolic mode. J Exp Med 196(10):1387-1392, 2002.
46. Lima F, Vico L, Lafage-Proust MH, van der Saag P, Alexandre C, Thomas T. Interactions between estrogen and mechanical strain effects on U2OS human osteosarcoma cells are not influenced by estrogen receptor type. Bone 35(5):1127-1135, 2004.
47. Liu X, Zhang X, Luo ZP. Strain-related collagen gene expression in human osteoblast-like cells. Cell Tissue Res 322(2):331-334, 2005.
48. Narutomi M, Nishiura T, Sakai T, Abe K, Ishikawa H. Cyclic mechanical strain induces interleukin-6 expression via prostaglandin E2 production by cyclooxygenase-2 in MC3T3-E1 osteoblast-like cells. J Oral Biosci 49(1):65-73, 2007.
49. Miyauchi A, Gotoh M, Kamioka H, Notoya K, Sekiya H, Takagi Y, Yoshimoto Y, Ishikawa H, Chihara K, Takano-Yamamoto T, Fujita T, Mikuni-Takagaki Y. V3 integrin ligands enhance volume-sensitive calcium influx in mechanically stretched osteocytes. J Bone Miner Metab 24(6):498-504, 2006.
50. Motokawa M, Kaku M, Tohma Y, Kawata T, Fujita T, Kohno S, Tsutsui K, Ohtani J, Tenjo K, Shigekawa M, Kamada H, Tanne K. Effects of cyclic tensile forces on the expression of vascular
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endothelial growth factor (VEGF) and macrophage-colony-stimulating factor (M-CSF) in murine osteoblastic MC3T3-E1 cells. J Dent Res 84(5):422-427, 2005.
51. Myers KA, Rattner JB, Shrive NG, Hart DA. Osteoblast-like cells and fluid flow: cytoskeleton-dependent shear sensitivity. Biochem Biophys Res Commun 364(2):214-219, 2007.
52. Plotkin LI, Mathov I, Aguirre JI, Parfitt AM, Manolagas SC, Bellido T. Mechanical stimulation prevents osteocyte apoptosis: requirement of integrins, Src kinases, and ERKs. Am J Physiol Cell Physiol 289(3):C633-643, 2005.
53. Qi J, Chi L, Faber J, Koller B, Banes AJ. ATP reduces gel compaction in osteoblast-populated collagen gels. J Appl Physiol 102(3):1152-60, 2007.
54. Qi J, Chi L, Wang J, Sumanasinghe R, Wall M, Tsuzaki M, Banes AJ. Modulation of collagen gel compaction by extracellular ATP is MAPK and NF-B pathways dependent. Exp Cell Res 315(11):1990-2000, 2009.
55. Rath B, Springorum HR, Deschner J, Luring C, Tingart M, Grifka J, Schaumburger J, Grassel S. Regulation of gene expression in articular cells is influenced by biomechanical loading. Central European Journal of Medicine 2012.
56. Robinson JA, Chatterjee-Kishore M, Yaworsky PJ, Cullen DM, Zhao W, Li C, Kharode Y, Sauter L, Babij P, Brown EL, Hill AA, Akhter MP, Johnson ML, Recker RR, Komm BS, Bex FJ. Wnt/-catenin signaling is a normal physiological response to mechanical loading in bone. J Biol Chem 281(42):31720-31728, 2006.
57. Sano S, Okawa A, Nakajima A, Tahara M, Fujita K, Wada Y, Yamazaki M, Moriya H, Sasho T. Identification of Pip4k2 as a mechanical stimulus responsive gene and its expression during musculoskeletal tissue healing. Cell Tissue Res 323(2):245-252, 2006.
58. Shi GX, Zheng XF, Zhu C, Li B, Wang YR, Jiang SD, Jiang LS. Evidence of the role of R-spondin 1 and its receptor Lgr4 in the transmission of mechanical stimuli to biological signals for bone formation. Int J Mol Sci 18(3), pii: E564, 2017.
59. Siddhivarn C, Banes A, Champagne C, Riche EL, Weerapradist W, Offenbacher S. Prostaglandin D2 pathway and peroxisome proliferator-activated receptor -1 expression are induced by mechanical loading in an osteoblastic cell line. J Periodontal Res 41(2):92-100, 2006.
60. Siddhivarn C, Banes A, Champagne C, Riche EL, Weerapradist W, Offenbacher S. Mechanical loading and Δ12prostaglandin J2 induce bone morphogenetic protein-2, peroxisome proliferator-activated receptor γ-1, and bone nodule formation in an osteoblastic cell line. J Periodontal Res 42(5):383-392, 2007.
61. Stanford CM, Stevens JW, Brand RA. Cellular deformation reversibly depresses RT-PCR detectable levels of bone-related mRNA. Journal of Biomechanics 28(12):1419-1427, 1995.
62. Sun Z, Tee BC. Molecular variations related to the regional differences in periosteal growth at the mandibular ramus. Anat Rec (Hoboken) 294(1):79-87, 2011.
63. Suzuki N, Yoshimura Y, Deyama Y, Suzuki K, Kitagawa Y. Mechanical stress directly suppresses osteoclast differentiation in RAW264.7 cells. Int J Mol Med 21(3):291-296, 2008.
64. Tang L, Lin Z, Li YM. Effects of different magnitudes of mechanical strain on osteoblasts in vitro. Biochem Biophys Res Commun 344(1):122-128, 2006.
65. Thompson MS, Epari DR, Bieler F, Duda GN. In vitro models for bone mechanobiology: applications in bone regeneration and tissue engineering. Proc Inst Mech Eng H 224(12):1533-1541, 2010.
66. Tomlinson RE, Li Z, Li Z, Minichiello L, Riddle RC, Venkatesan A, Clemens TL. NGF-TrkA signaling in sensory nerves is required for skeletal adaptation to mechanical loads in mice. Proc Natl Acad Sci U S A 114(18):E3632-E3641, 2017.
67. Toyoshita Y, Iida S, Koshino H, Hirai T, Yokoyama A. CYP24 promoter activity is affected by mechanical stress and mitogen-activated protein kinase in MG63 osteoblast-like cells. Nihon Hotetsu Shika Gakkai Zasshi 52(2):171-174, 2008.
68. Vadiakas GP, Banes AJ. Verapamil decreases cyclic load-induced calcium incorporation in ROS 17/2.8 osteosarcoma cell cultures. Matrix 12(6):439-447, 1992.
69. Visconti LA, Yen EH, Johnson RB. Effect of strain on bone nodule formation by rat osteogenic cells in vitro. Archives of Oral Biology 49(6):485-492, 2004.
70. Wang H, Sun W, Ma J, Pan Y, Wang L, Zhang W. Polycystin-1 mediates mechanical strain-induced osteoblastic mechanoresponses via potentiation of intracellular calcium and Akt/β-catenin pathway. PLoS One 9(3):e91730, 2014.
FLEXCELL® INTERNATIONAL CORPORATION
6
71.Wu Y, Zhang X, Zhang P, Fang B, Jiang L. Intermittent traction stretch promotes the osteoblasticdifferentiation of bone mesenchymal stem cells by the ERK1/2-activated Cbfa1 pathway. Connect Tissue Res53(6):451-9, 2012.
72.Yamamoto N, Fukuda K, Matsushita T, Matsukawa M, Hara F, Hamanishi C. Cyclic tensile stretchstimulates the release of reactive oxygen species from osteoblast-like cells. Calcif Tissue Int 76(6):433-8,2005.
73.Yu HC, Wu TC, Chen MR, Liu SW, Chen JH, Lin Xiao LW, Yang M, Dong J, Xie H, Sui GL, He YL,Lei JX, Liao EY, Yuan X. Stretch-inducible expression of connective tissue growth factor (CTGF) in humanosteoblasts-like cells is mediated by PI3K-JNK pathway. Cell Physiol Biochem 28(2):297-304, 2011.
74.Yu KW, Yao CC, Jeng JH, Shieh HY, Chen YJ. Periostin inhibits mechanical stretch-induced apoptosis inosteoblast-like MG-63 cells. J Formos Med Assoc 2018 Jan 3. pii: S0929-6646(17)30820-3. doi:10.1016/j.jfma.2017.12.008. [Epub ahead of print].
75.Zeng Z, Jing D, Zhang X, Duan Y, Xue F. Cyclic mechanical stretch promotes energy metabolism inosteoblast-like cells through an mTOR signaling-associated mechanism. Int J Mol Med 36(4):947-56, 2015.
76.Zeng Z, Yin X, Zhang X, Jing D, Feng X. Cyclic stretch enhances bone morphogenetic protein-2-inducedosteoblastic differentiation through the inhibition of Hey1. Int J Mol Med 36(5):1273-1281, 2015.
77.Zhang C, Liang G, Zhang Y, Hu Y. Response to dynamic strain in human periosteal cells grown in vitro.Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 23(3):546-550, 2006.
78.Zhu J, Zhang X, Wang C, Peng X, Zhang X. Different magnitudes of tensile strain induce humanosteoblasts differentiation associated with the activation of ERK1/2 phosphorylation. Int J Mol Sci9(12):2322-2332, 2008.
79.Ziambaras K, Lecanda F, Steinberg TH, Civitelli R. Cyclic stretch enhances gap junctional communicationbetween osteoblastic cells. J Bone Miner Res 13(2):218-28, 1998.
80.Zuo B, Zhu J, Li J, Wang C, Zhao X, Cai G, Li Z, Peng J, Wang P, Shen C, Huang Y, Xu J, Zhang X,Chen X. microRNA-103a functions as a mechanosensitive microRNA to inhibit bone formation throughtargeting Runx2. J Bone Miner Res 30(2):330-45, 2015.
CARDIOVASCULATURE
CARDIOMYOCYTES AND FIBROBLASTS
1.Alibin CP, Kopilas MA, Anderson HD. Suppression of cardiac myocyte hypertrophy by conjugated linoleicacid: role of peroxisome proliferator-activated receptors  and . J Biol Chem 283(16):10707-10715, 2008.
2.Anderson HD, Wang F, Gardner DG. Role of the epidermal growth factor receptor in signaling strain-dependent activation of the brain natriuretic peptide gene. J Biol Chem 279(10):9287-9297, 2004.
3.Argento G, de Jonge N, Söntjens SH, Oomens CW, Bouten CV, Baaijens FP. Modeling the impact ofscaffold architecture and mechanical loading on collagen turnover in engineered cardiovascular tissues.Biomech Model Mechanobiol 14(3):603-13, 2015.
4.Askevold ET, Aukrust P, Nymo SH, Lunde IG, Kaasbøll OJ, Aakhus S, Florholmen G, Ohm IK, StrandME, Attramadal H, Fiane A, Dahl CP, Finsen AV, Vinge LE, Christensen G, Yndestad A, Gullestad L,Latini R, Masson S, Tavazzi L; GISSI-HF Investigators, Ueland T. The cardiokine secreted Frizzled-related protein 3, a modulator of Wnt signalling, in clinical and experimental heart failure. J Intern Med275(6):621-30, 2014.
5.Baba HA, Stypmann J, Grabellus F, Kirchhof P, Sokoll A, Schafers M, Takeda A, Wilhelm MJ, ScheldHH, Takeda N, Breithardt G, Levkau B. Dynamic regulation of MEK/Erks and Akt/GSK-3 in human end-stage heart failure after left ventricular mechanical support: myocardial mechanotransduction-sensitivity as apossible molecular mechanism. Cardiovascular Research 59(2):390-399, 2003.
6.Boateng SY, Belin RJ, Geenen DL, Margulies KB, Martin JL, Hoshijima M, de Tombe PP, Russell B.Cardiac dysfunction and heart failure are associated with abnormalities in the subcellular distribution andamounts of oligomeric muscle LIM protein. Am J Physiol Heart Circ Physiol 292(1):H259-H269, 2007.
7.Boateng SY, Lateef SS, Mosley W, Hartman TJ, Hanley L, Russell B. RGD and YIGSR synthetic peptidesfacilitate cellular adhesion identical to that of laminin and fibronectin but alter the physiology of neonatalcardiac myocytes. Am J Physiol Cell Physiol 288(1):C30-C38, 2005.
8.Boateng SY, Senyo SE, Qi L, Goldspink PH, Russell B. Myocyte remodeling in response to hypertrophicstimuli requires nucleocytoplasmic shuttling of muscle LIM protein. J Mol Cell Cardiol 47(4):426-35, 2009.
FLEXCELL® INTERNATIONAL CORPORATION
7
9. Boerboom RA, Rubbens MP, Driessen NJ, Bouten CV, Baaijens FP. Effect of strain magnitude on the tissue properties of engineered cardiovascular constructs. Annals of Biomedical Engineering 36(2):244–253, 2008.
10. Boerma M, van der Wees CG, Vrieling H, Svensson JP, Wondergem J, van der Laarse A, Mullenders LH, van Zeeland AA. Microarray analysis of gene expression profiles of cardiac myocytes and fibroblasts after mechanical stress, ionising or ultraviolet radiation. BMC Genomics 6(1):6, 2005.
11. Blaauw E, van Nieuwenhoven FA, Willemsen P, Delhaas T, Prinzen FW, Snoeckx LH, van Bilsen M, van der Vusse GJ. Stretch-induced hypertrophy of isolated adult rabbit cardiomyocytes. Am J Physiol Heart Circ Physiol 299(3):H780-H787, 2010.
12. Cao L, Gardner DG. Natriuretic peptides inhibit DNA synthesis in cardiac fibroblasts. Hypertension 25(2):227-234, 1995.
13. Cheng WP, Wang BW, Lo HM, Shyu KG. Mechanical stretch induces apoptosis regulator TRB3 in cultured cardiomyocytes and volume-overloaded heart. PLoS One 10(4):e0123235, 2015.
14. Choudhary R, Palm-Leis A, Scott RC 3rd, Guleria RS, Rachut E, Baker KM, Pan J. All-trans retinoic acid prevents development of cardiac remodeling in aortic banded rats by inhibiting the renin-angiotensin system. Am J Physiol Heart Circ Physiol 294(2):H633-H644, 2008.
15. Chua SK, Wang BW, Lien LM, Lo HM, Chiu CZ, Shyu KG. Mechanical stretch inhibits microRNA499 via p53 to regulate calcineurin-A expression in rat cardiomyocytes. PLoS One 11(2):e0148683, 2016.
16. de Jonge HW, Dekkers DH, Tilly BC, Lamers JM. Cyclic stretch and endothelin-1 mediated activation of chloride channels in cultured neonatal rat ventricular myocytes. Clin Sci (Lond) 103(48):148S-151S, 2002.
17. de Jonge N, Kanters FM, Baaijens FP, Bouten CV. Strain-induced collagen organization at the micro-level in fibrin-based engineered tissue constructs. Ann Biomed Eng 41(4):763-74, 2013.
18. De Jong AM, Maass AH, Oberdorf-Maass SU, De Boer RA, Van Gilst WH, Van Gelder IC. Cyclical stretch induces structural changes in atrial myocytes. J Cell Mol Med 17(6):743-53, 2013.
19. Dhein S, Schreiber A, Steinbach S, Apel D, Salameh A, Schlegel F, Kostelka M, Dohmen PM, Mohr FW. Mechanical control of cell biology. Effects of cyclic mechanical stretch on cardiomyocyte cellular organization. Prog Biophys Mol Biol 115(2-3):93-102, 2014.
20. Drolet MC, Desbiens-Brassard V, Roussel E, Tu V, Couet J, Arsenault M. Blockade of the acute activation of mTOR complex 1 decreases hypertrophy development in rats with severe aortic valve regurgitation. Springerplus 4:435, 2015.
21. Espinoza-Derout J, Wagner M, Shahmiri K, Mascareno E, Chaqour B, Siddiqui MA. Pivotal role of cardiac lineage protein-1 (CLP-1) in transcriptional elongation factor P-TEFb complex formation in cardiac hypertrophy. Cardiovasc Res 75(1):129-138, 2007.
22. Facundo HT, Brainard RE, Watson LJ, Ngoh GA, Hamid T, Prabhu SD, Jones SP. O-GlcNAc signaling is essential for NFAT-mediated transcriptional reprogramming during cardiomyocyte hypertrophy. Am J Physiol Heart Circ Physiol 302(10):H2122-30, 2012.
23. Fan D, Takawale A, Basu R, Patel V, Lee J, Kandalam V, Wang X, Oudit GY, Kassiri Z. Differential role of TIMP2 and TIMP3 in cardiac hypertrophy, fibrosis, and diastolic dysfunction. Cardiovasc Res 103(2):268-80, 2014.
24. Fan D, Takawale A, Shen M, Samokhvalov V, Basu R, Patel V, Wang X, Fernandez-Patron C, Seubert JM, Oudit GY, Kassiri Z. A disintegrin and metalloprotease-17 regulates pressure overload-induced myocardial hypertrophy and dysfunction through proteolytic processing of integrin β1. Hypertension 68(4):937-48, 2016.
25. Feng H, Gerilechaogetu F, Golden HB, Nizamutdinov D, Foster DM, Glaser SS, Dostal DE. p38α MAPK inhibits stretch-induced JNK activation in cardiac myocytes through MKP-1. Int J Cardiol 203:145-55, 2016.
26. Földes G, Mioulane M, Wright JS, Liu AQ, Novak P, Merkely B, Gorelik J, Schneider MD, Ali NN, Harding SE. Modulation of human embryonic stem cell-derived cardiomyocyte growth: a testbed for studying human cardiac hypertrophy? J Mol Cell Cardiol 50(2):367-376, 2011.
27. Fu L, Wei CC, Powell PC, Bradley WE, Ahmad S, Ferrario CM, Collawn JF, Dell'Italia LJ. Increased fibroblast chymase production mediates procollagen autophagic digestion in volume overload. J Mol Cell Cardiol 92:1-9, 2016.
28. Funari BJ, Witt MR, Clause KM, Keller BB, Tobita K, Ralphe JC. The impact of energy substrate on contractile performance in a neonatal rat engineered cardiac tissue model [abstract]. Pediatric Academic Societies Annual Meeting, Toronto, Canada, 2007.
29. Gardner DG, Newman ED, Nakamura KK, Nguyen KP. Endothelin increases the synthesis and secretion of atrial natriuretic peptide in neonatal rat cardiocytes. Am J Physiol Endocrinol Metab 261:E177-E182, 1991.
FLEXCELL® INTERNATIONAL CORPORATION
8
30. Guichard JL, Benavides GA, Ballinger S, Darley-Usmar VM, Dell_Italia LJ. Mitochondrial genetic background modulatesthe mitochondrial and cytoskeletal response to cyclical stretch in isolated adult cardiomyocytes [abstract]. Journal of the American College of Cardiology 63(12):A869, 2014.
31. Gupta S, Sen S. Myotrophin-kB DNA interaction in the initiation process of cardiac hypertrophy. Biochimica et Biophysica Acta (BBA)/Molecular Cell Research 1589(3):247-260, 2002.
32. Harada M, Saito Y, Nakagawa O, Miyamoto Y, Ishikawa M, Kuwahara K, Ogawa E, Nakayama M, Kamitani S, Hamanaka I, Kajiyama N, Masuda I, Itoh H, Tanaka I, Nakao K. Role of cardiac nonmyocytes in cyclic mechanical stretch-induced myocyte hypertrophy. Heart Vessels Suppl 12:198-200, 1997.
33. Hariharan N, Ikeda Y, Hong C, Alcendor RR, Usui S, Gao S, Maejima Y, Sadoshima J. Autophagy plays an essential role in mediating regression of hypertrophy during unloading of the heart. PLoS One 8(1):e51632, 2013.
34. Heineke J, Ruetten H, Willenbockel C, Gross SC, Naguib M, Schaefer A, Kempf T, Hilfiker-Kleiner D, Caroni P, Kraft T, Kaiser RA, Molkentin JD, Drexler H, Wollert KC. Attenuation of cardiac remodeling after myocardial infarction by muscle LIM protein-calcineurin signaling at the sarcomeric Z-disc. Proc Natl Acad Sci U S A 102(5):1655-1660, 2005.
35. Hilfiker-Kleiner D, Kaminski K, Kaminska A, Fuchs M, Klein G, Podewski E, Grote K, Kiian I, Wollert KC, Hilfiker A, Drexler H. Regulation of proangiogenic factor CCN1 in cardiac muscle: impact of ischemia, pressure overload, and neurohumoral activation. Circulation 109(18):2227-2233, 2004.
36. Hooper CL, Dash PR, Boateng SY. Lipoma preferred partner is a mechanosensitive protein regulated by nitric oxide in the heart. FEBS Open Bio 2:135-44, 2012.
37. Husse B, Sopart A, Isenberg G. Cyclical mechanical stretch-induced apoptosis in myocytes from young rats but necrosis in myocytes from old rats. Am J Physiol Heart Circ Physiol 285:1521-1527, 2003.
38. Kartasalo K, Pölönen RP, Ojala M, Rasku J, Lekkala J, Aalto-Setälä K, Kallio P. CytoSpectre: a tool for spectral analysis of oriented structures on cellular and subcellular levels. BMC Bioinformatics 16:344, 2015.
39. Kasmi KE, Myers C, Flockton A, Riddle S, McKeon BA, Frid M, Brodsky K, Eltzschig H, Stenmark KR. Mechanical stretch combines with adventitial fibroblast-derived signals to promote macrophage activation through metabolic reprogramming in vascular remodeling [abstract]. Am J Respir Crit Care Med 193:A2227, 2016.
40. Koitabashi N, Arai M, Kogure S, Niwano K, Watanabe A, Aoki Y, Maeno T, Nishida T, Kubota S, Takigawa M, Kurabayashi M. Increased connective tissue growth factor relative to brain natriuretic peptide as a determinant of myocardial fibrosis. Hypertension 49(5):1120-1127, 2007.
41. Koivisto E, Jurado Acosta A, Moilanen AM, Tokola H, Aro J, Pennanen H, Säkkinen H, Kaikkonen L, Ruskoaho H, Rysä J. Characterization of the regulatory mechanisms of activating transcription factor 3 by hypertrophic stimuli in rat cardiomyocytes. PLoS One 9(8):e105168, 2014.
42. Lal H, Verma SK, Golden HB, Foster DM, Smith M, Dostal DE. Stretch-induced regulation of angiotensinogen gene expression in cardiac myocytes and fibroblasts: opposing roles of JNK1/2 and p38 MAP kinases. J Mol Cell Cardiol 45(6):770-778, 2008.
43. Lal H, Verma SK, Smith M, Guleria RS, Lu G, Foster DM, Dostal DE. Stretch-induced MAP kinase activation in cardiac myocytes: differential regulation through 1-integrin and focal adhesion kinase. J Mol Cell Cardiol 43(2):137-147, 2007.
44. Lateef SS, Boateng S, Ahluwalia N, Hartman TJ, Russell B, Hanley L. Three-dimensional chemical structures by protein functionalized micron-sized beads bound to polylysine-coated silicone surfaces. J Biomed Mater Res A 72(4):373-380, 2005.
45. Lateef SS, Boateng S, Hartman TJ, Crot CA, Russell B, Hanley L. GRGDSP peptide-bound silicone membranes withstand mechanical flexing in vitro and display enhanced fibroblast adhesion. Biomaterials 23(15):3159-3168, 2002.
46. Lee EL, Watson KC, von Recum HA. Contractile protein and extracellular matrix secretion of cell monolayer sheets following cyclic stretch. Cardiovascular Engineering and Technology 3(3):302-310, 2012.
47. Liang F, Atakilit A, Gardner DG. Integrin dependence of brain natriuretic peptide gene promoter activation by mechanical strain. J Biol Chem 275(27):20355-20360, 2000.
48. Liang F, Gardner DG. Autocrine/paracrine determinants of strain-activated brain natriuretic peptide gene expression in cultured cardiac myocytes. J Biol Chem 273(23):14612-14619, 1998.
49. Liang F, Gardner DG. Mechanical strain activates BNP gene transcription through a p38/NF-B-dependent mechanism. J Clin Invest 104(11):1603-1612, 1999.
FLEXCELL® INTERNATIONAL CORPORATION
9
50. Liang F, Kovacic-Milivojevic B, Chen S, Cui J, Roediger F, Intengan H, Gardner DG. Signaling mechanisms underlying strain-dependent brain natriuretic peptide gene transcription. Can J Physiol Pharmacol 79(8):640-645, 2001.
51. Liang F, Lu S, Gardner DG. Endothelin-dependent and -independent components of strain-activated brain natriuretic peptide gene transcription require extracellular signal regulated kinase and p38 mitogen-activated protein kinase. Hypertension 35(1 Pt 2):188-192, 2000.
52. Liang F, Wu J, Garami M, Gardner DG. Mechanical strain increases expression of the brain natriuretic peptide gene in rat cardiac myocytes. J Biol Chem 272(44):28050-28056, 1997.
53. Liang YJ, Lai LP, Wang BW, Juang SJ, Chang CM, Leu JG, Shyu KG. Mechanical stress enhances serotonin 2B receptor modulating brain natriuretic peptide through nuclear factor-B in cardiomyocytes. Cardiovasc Res 72(2):303-12, 2006.
54. Lin YH, Swanson ER, Li J, Mkrtschjan MA, Russell B. Cyclic mechanical strain of myocytes modifies CapZβ1 post translationally via PKCε. J Muscle Res Cell Motil 36(4-5):329-37, 2015.
55. Lindahl GE, Chambers RC, Papakrivopoulou J, Dawson SJ, Jacobsen MC, Bishop JE, Laurent GJ. Activation of fibroblast procollagen 1(I) transcription by mechanical strain is transforming growth factor--dependent and involves increased binding of CCAAT-binding factor (CBF/NF-Y) at the proximal promoter. J Biol Chem 277(8):6153-6161, 2002.
56. Malhotra R, D'Souza KM, Staron ML, Birukov KG, Bodi I, Akhter SA. Gq-mediated activation of GRK2 by mechanical stretch in cardiac myocytes: the role of protein kinase C. J Biol Chem 285(18):13748-13760, 2010.
57. Marin TM, Clemente CF, Santos AM, Picardi PK, Pascoal VD, Lopes-Cendes I, Saad MJ, Franchini KG. Shp2 negatively regulates growth in cardiomyocytes by controlling focal adhesion kinase/Src and mTOR pathways. Circ Res 103(8):813-824, 2008.
58. Mauretti A, Bax NA, van Marion MH, Goumans MJ, Sahlgren C, Bouten CV. Cardiomyocyte progenitor cell mechanoresponse unrevealed: strain avoidance and mechanosome development. Integr Biol (Camb) 8(9):991-1001, 2016.
59. Miller CE, Donlon KJ, Toia L, Wong CL, Chess PR. Cyclic strain induces proliferation of cultured embryonic heart cells. In Vitro Cell Dev Biol Anim 36(10):633-639, 2000.
60. Nadruz W Jr, Corat MA, Marin TM, Guimaraes Pereira GA, Franchini KG. Focal adhesion kinase mediates MEF2 and c-Jun activation by stretch: role in the activation of the cardiac hypertrophic genetic program. Cardiovasc Res 68(1):87-97, 2005.
61. Nguyen MD, Tinney JP, Ye F, Elnakib AA, Yuan F, El-Baz A, Sethu P, Keller BB, Giridharan GA. Effects of physiologic mechanical stimulation on embryonic chick cardiomyocytes using a microfluidic cardiac cell culture model. Anal Chem 87(4):2107-13, 2015.
62. Niu A, Wang B, Li YP. TNFα shedding in mechanically stressed cardiomyocytes is mediated by Src activation of TACE. J Cell Biochem 116(4):559-65, 2015.
63. Palm-Leis A, Singh US, Herbelin BS, Olsovsky GD, Baker KM, Pan J. Mitogen-activated protein kinases and mitogen-activated protein kinase phosphatases mediate the inhibitory effects of all-trans retinoic acid on the hypertrophic growth of cardiomyocytes. J Biol Chem 279(52):54905-54917, 2004.
64. Pan J, Singh US, Takahashi T, Oka Y, Palm-Leis A, Herbelin BS, Baker KM. PKC mediates cyclic stretch-induced cardiac hypertrophy through Rho family GTPases and mitogen-activated protein kinases in cardiomyocytes. J Cell Physiol 202(2):536-553, 2005.
65. Pedrozo Z, Criollo A, Battiprolu PK, Morales CR, Contreras-Ferrat A, Fernández C, Jiang N, Luo X, Caplan MJ, Somlo S, Rothermel BA, Gillette TG, Lavandero S, Hill JA. Polycystin-1 is a cardiomyocyte mechanosensor that governs L-type Ca2+ channel protein stability. Circulation 131(24):2131-42, 2015.
66. Persoon-Rothert M, van der Wees KG, van der Laarse A. Mechanical overload-induced apoptosis: a study in cultured neonatal ventricular myocytes and fibroblasts. Mol Cell Biochem 241(1-2):115-24, 2002.
67. Pikkarainen S, Tokola H, Kerkela R, Ilves M, Makinen M, Orzechowski HD, Paul M, Vuolteenaho O, Ruskoaho H. Inverse regulation of preproendothelin-1 and endothelin-converting enzyme-1 genes in cardiac cells by mechanical load. Am J Physiol Regul Integr Comp Physiol 290(6):R1639-R1645, 2006.
68. Pikkarainen S, Tokola H, Kerkela R, Majalahti-Palviainen T, Vuolteenaho O, Ruskoaho H. Endothelin-1-specific activation of B-type natriuretic peptide gene via p38 mitogen-activated protein kinase and nuclear ETS factors. J Biol Chem 278(6):3969-3975, 2003.
69. Pikkarainen S, Tokola H, Majalahti-Palviainen T, Kerkela R, Hautala N, Bhalla SS, Charron F, Nemer M, Vuolteenaho O, Ruskoaho H. GATA-4 is a nuclear mediator of mechanical stretch-activated hypertrophic program. J Biol Chem 278(26):23807-23816, 2003.
FLEXCELL® INTERNATIONAL CORPORATION
10
70.Pimentel DR, Amin JK, Xiao L, Miller T, Viereck J, Oliver-Krasinski J, Baliga R, Wang J, Siwik DA,Singh K, Pagano P, Colucci WS, Sawyer DB. Reactive oxygen species mediate amplitude-dependenthypertrophic and apoptotic responses to mechanical stretch in cardiac myocytes. Circ Res 89(5):453-460,2001.
71.Prante C, Milting H, Kassner A, Farr M, Ambrosius M, Schön S, Seidler DG, Banayosy AE, Körfer R,Kuhn J, Kleesiek K, Götting C. Transforming growth factor 1-regulated xylosyltransferase I activity inhuman cardiac fibroblasts and its impact for myocardial remodeling. J Biol Chem 282(36):26441-26449,2007.
72.Raval KK, Tao R, White BE, De Lange WJ, Koonce CH, Yu J, Kishnani PS, Thomson JA, Mosher DF,Ralphe JC, Kamp TJ. Pompe disease results in a Golgi-based glycosylation deficit in human inducedpluripotent stem cell-derived cardiomyocytes. J Biol Chem 290(5):3121-36, 2015.
73.Rubbens MP, Driessen-Mol A, Boerboom RA, Koppert MM, van Assen HC, TerHaar Romeny BM,Baaijens FP, Bouten CV. Quantification of the temporal evolution of collagen orientation in mechanicallyconditioned engineered cardiovascular tissues. Ann Biomed Eng 37(7):1263-1272, 2009.
74.Ruwhof C, van Wamel AE, Egas JM, van der Laarse A. Cyclic stretch induces the release of growthpromoting factors from cultured neonatal cardiomyocytes and cardiac fibroblasts. Mol Cell Biochem 208(1-2):89-98, 2000.
75.Ruwhof C, van Wamel AE, van der Valk LJ, Schrier PI, van der Laarse A. Direct, autocrine andparacrine effects of cyclic stretch on growth of myocytes and fibroblasts isolated from neonatal rat ventricles.Arch Physiol Biochem 109(1):10-17, 2001.
76.Ruwhof C, van Wamel JT, Noordzij LA, Aydin S, Harper JC, van der Laarse A. Mechanical stressstimulates phospholipase C activity and intracellular calcium ion levels in neonatal rat cardiomyocytes. CellCalcium 29(2):73-83, 2001.
77.Säkkinen H, Aro J, Kaikkonen L, Ohukainen P, Näpänkangas J, Tokola H, Ruskoaho H, Rysä J.Mitogen-activated protein kinase p38 target regenerating islet-derived 3γ expression is upregulated in cardiacinflammatory response in the rat heart. Physiol Rep 4(20), 2016. pii: e12996.
78.Salameh A, Apel D, Gonzalez Casanova J, von Salisch S, Mohr FW, Daehnert I, Dhein S. On thedifferent roles of AT1 and AT2 receptors in stretch-induced changes of connexin43 expression andlocalisation. Pflugers Arch 464(5):535-47, 2012.
79.Senyo SE, Koshman YE, Russell B. Stimulus interval, rate and direction differentially regulatephosphorylation for mechanotransduction in neonatal cardiac myocytes. FEBS Lett 581(22):4241-4247, 2007.
80.Shyu KG, Ko WH, Yang WS, Wang BW, Kuan P. Insulin-like growth factor-1 mediates stretch-inducedupregulation of myostatin expression in neonatal rat cardiomyocytes. Cardiovascular Research 68(3):405-414, 2005.
81.Sil P, Gupta S, Young D, Sen S. Regulation of myotrophin gene by pressure overload and stretch. Mol CellBiochem 262(1-2):79-89, 2004.
82.Simmons CA, Nikolovski J, Thornton AJ, Matlis S, Mooney DJ. Mechanical stimulation and mitogen-activated protein kinase signaling independently regulate osteogenic differentiation and mineralization bycalcifying vascular cells. Journal of Biomechanics 37(10):1531-1541, 2004.
83.Skurk C, Izumiya Y, Maatz H, Razeghi P, Shiojima I, Sandri M, Sato K, Zeng L, Schiekofer S,Pimentel D, Lecker S, Taegtmeyer H, Goldberg AL, Walsh K. The FOXO3a transcription factor regulatescardiac myocyte size downstream of AKT signaling. J Biol Chem 280(21):20814-20823, 2005.
84.Sun X, Nunes SS. Bioengineering approaches to mature human pluripotent stem cell-derived cardiomyocytes.Front Cell Dev Biol 5:19, 2017.
85.Swildens J, de Vries AA, Li Z, Umar S, Atsma DE, Schalij MJ, van der Laarse A. Integrin stimulationfavors uptake of macromolecules by cardiomyocytes in vitro. Cell Physiol Biochem 26(6):999-1010, 2010.
86.Tobita K, Garrison JB, Keller BB. Differential effects of cyclic stretch on embryonic ventricularcardiomyocyte and non-cardiomyocyte orientation. In: Cardiovascular Development and CongenitalMalformations: Molecular & Genetic Mechanisms, Edited by Artman M, Benson DW, Srivastava D,Nakazawa M. Blackwell Futura Publishing:177-179, 2005.
87.Tomanek RJ, Zheng W. Role of growth factors in coronary morphogenesis. Tex Heart Inst J 29(4):250-254,2002.
88.Tornatore TF, Dalla Costa AP, Clemente CF, Judice C, Rocco SA, Calegari VC, Cardoso L, CardosoAC, Gonçalves A Jr, Franchini KG. A role for focal adhesion kinase in cardiac mitochondrial biogenesisinduced by mechanical stress. Am J Physiol Heart Circ Physiol 300(3):H902-H912, 2011.
FLEXCELL® INTERNATIONAL CORPORATION
11
89. Torsoni AS, Constancio SS, Nadruz W, Hanks SK, Franchini KG. Focal adhesion kinase is activated and mediates the early hypertrophic response to stretch in cardiac myocytes. Circ Res 93(2):140-147, 2003.
90. Torsoni AS, Marin TM, Velloso LA, Franchini KG. RhoA/ROCK signaling is critical to FAK activation by cyclic stretch in cardiac myocytes. Am J Physiol Heart Circ Physiol 289(4):H1488-H1496, 2005.
91. Tsai CT, Chiang FT, Tseng CD, Yu CC, Wang YC, Lai LP, Hwang JJ, Lin JL. Mechanical stretch of atrial myocyte monolayer decreases sarcoplasmic reticulum calcium adenosine triphosphatase expression and increases susceptibility to repolarization alternans. J Am Coll Cardiol 58(20):2106-2115, 2011.
92. Tulloch NL, Muskheli V, Razumova MV, Korte FS, Regnier M, Hauch KD, Pabon L, Reinecke H, Murry CE. Growth of engineered human myocardium with mechanical loading and vascular coculture. Circ Res 109(1):47-59, 2011.
93. Tyagi SC, Lewis K, Pikes D, Marcello A, Mujumdar VS, Smiley LM, Moore CK. Stretch-induced membrane type matrix metalloproteinase and tissue plasminogen activator in cardiac fibroblast cells. J Cell Physiol 176(2):374-382, 1998.
94. van Kesteren CA, Saris JJ, Dekkers DH, Lamers JM, Saxena PR, Schalekamp MA, Danser AH. Cultured neonatal rat cardiac myocytes and fibroblasts do not synthesize renin or angiotensinogen: evidence for stretch-induced cardiomyocyte hypertrophy independent of angiotensin II. Cardiovascular Research 43(1):148-156, 1999.
95. van Wamel AJ, Ruwhof C, van der Valk-Kokshoom LE, Schrier PI, van der Laarse A. The role of angiotensin II, endothelin-1 and transforming growth factor- as autocrine/paracrine mediators of stretch-induced cardiomyocyte hypertrophy. Mol Cell Biochem 218(1-2):113-124, 2001.
96. van Wamel AJ, Ruwhof C, van der Valk-Kokshoorn LJ, Schrier PI, van der Laarse A. Stretch-induced paracrine hypertrophic stimuli increase TGF-1 expression in cardiomyocytes. Mol Cell Biochem 236(1-2):147-153, 2002.
97. van Wamel JE, Ruwhof C, van der Valk-Kokshoorn EJ, Schrier PI, van der Laarse A. Rapid gene transcription induced by stretch in cardiac myocytes and fibroblasts and their paracrine influence on stationary myocytes and fibroblasts. Pflugers Arch 439(6):781-788, 2000.
98. Wang BW, Hung HF, Chang H, Kuan P, Shyu KG. Mechanical stretch enhances the expression of resistin gene in cultured cardiomyocytes via tumor necrosis factor-. Am J Physiol Heart Circ Physiol 293(4):H2305-H2312, 2007.
99. Wang B, Wu G, Cheng K, Shyue K. Mechanical stretch via transforming growth factor-β1 activates microRNA-208a to regulate hypertrophy in cultured rat cardiac myocytes. Journal of the Formosan Medical Association, 2013. (10.1016/j.jfma.2013.01.002).
100. Watson CJ, Phelan D, Collier P, Horgan S, Glezeva N, Cooke G, Xu M, Ledwidge M, McDonald K, Baugh JA. Extracellular matrix sub-types and mechanical stretch impact human cardiac fibroblast responses to transforming growth factor . Connect Tissue Res 55(3):248-56, 2014.
101. Watson CJ, Phelan D, Xu M, Collier P, Neary R, Smolenski A, Ledwidge M, McDonald K, Baugh J. Mechanical stretch up-regulates the B-type natriuretic peptide system in human cardiac fibroblasts: a possible defense against transforming growth factor-β mediated fibrosis. Fibrogenesis Tissue Repair 5(1):9, 2012.
102. Wei CC, Chen Y, Powell LC, Zheng J, Shi K, Bradley WE, Powell PC, Ahmad S, Ferrario CM, Dell'Italia LJ. Cardiac kallikrein-kinin system is upregulated in chronic volume overload and mediates an inflammatory induced collagen loss. PLoS One 7(6):e40110, 2012.
103. Wu CK, Su MY, Lee JK, Chiang FT, Hwang JJ, Lin JL, Chen JJ, Liu FT, Tsai CT. Galectin-3 level and the severity of cardiac diastolic dysfunction using cellular and animal models and clinical indices. Sci Rep 5:17007, 2015.
104. Wu CK, Wang YC, Lee JK, Chang SN, Su MY, Yeh HM, Su MJ, Chen JJ, Chiang FT, Hwang JJ, Lin JL, Tsai CT. Connective tissue growth factor and cardiac diastolic dysfunction: human data from the Taiwan diastolic heart failure registry and molecular basis by cellular and animal models. Eur J Heart Fail 16(2):163-72, 2014.
105. Xi YT, Bai XJ, Wu GR, Ma AQ. Centrifugal force stretcher a new of in vitro mechanical cell stimulator. Sheng Li Xue Bao 56(3):419-423, 2004.
106. Yokoyama T, Sekiguchi K, Tanaka T, Tomaru K, Arai M, Suzuki T, Nagai R. Angiotensin II and mechanical stretch induce production of tumor necrosis factor in cardiac fibroblasts. Am J Physiol Heart Circ Physiol 276:H1968-H1976, 1999.
107. Zheng W, Seftor EA, Meininger CJ, Hendrix MJ, Tomanek RJ. Mechanisms of coronary angiogenesis in response to stretch: role of VEGF and TGF-. Am J Physiol Heart Circ Physiol 280(2):H909-H917, 2001.
FLEXCELL® INTERNATIONAL CORPORATION
12
108. Zhou C, Ziegler C, Birder LA, Stewart AF, Levitan ES. Angiotensin II and stretch activate NADPH oxidase to destabilize cardiac Kv4.3 channel mRNA. Circ Res 98(8):1040-1047, 2006.
CARDIOVASCULAR ENDOTHELIAL CELLS
109. Ali MH, Pearlstein DP, Mathieu CE, Schumacker PT. Mitochondrial requirement for endothelial responses to cyclic strain: implications for mechanotransduction. Am J Physiol Lung Cell Mol Physiol 287(3):L486-L496, 2004.
110. Altalhi W, Sun X, Sivak JM, Husain M, Nunes SS. Diabetes impairs arterio-venous specification in engineered vascular tissues in a perivascular cell recruitment-dependent manner. Biomaterials 119:23-32, 2017.
111. Awolesi MA, Sessa WC, Sumpio BE. Cyclic strain upregulates nitric oxide synthase in cultured bovine aortic endothelial cells. J Clin Invest 96(3):1449-1454, 1995.
112. Azuma N, Duzgun SA, Ikeda M, Kito H, Akasaka N, Sasajima T, Sumpio BE. Endothelial cell response to different mechanical forces. J Vasc Surg 32(4):789-794, 2000.
113. Baker PN, Stranko CP, Davidge ST, Davies PS, Roberts JM. Mechanical stress eliminates the effects of plasma from patients with preeclampsia on endothelial cells. Am J Obstet Gynecol 174(2):730-6, 1996.
114. Brophy CM, Mills I, Rosales O, Isales C, Sumpio BE. Phospholipase C: a putative mechanotransducer for endothelial cell response to acute hemodynamic changes. Biochem Biophys Res Commun 190(2):576-581, 1993.
115. Cevallos M, Riha GM, Wang X, Yang H, Yan S, Li M, Chai H, Yao Q, Chen C. Cyclic strain induces expression of specific smooth muscle cell markers in human endothelial cells. Differentiation 74(9-10):552-561, 2006.
116. Chang H, Wang BW, Kuan P, Shyu KG. Cyclical mechanical stretch enhances angiopoietin-2 and Tie2 receptor expression in cultured human umbilical vein endothelial cells. Clin Sci (Lond) 104(4):421-428, 2003.
117. Cheng JJ, Chao YJ, Wang DL. Cyclic strain activates redox-sensitive proline-rich tyrosine kinase 2 (PYK2) in endothelial cells. J Biol Chem 277(50):48152-48157, 2002.
118. Cheng JJ, Wung BS, Chao YJ, Wang DL. Cyclic strain enhances adhesion of monocytes to endothelial cells by increasing intercellular adhesion molecule-1 expression. Hypertension 28(3):386-391, 1996.
119. Cheng JJ, Wung BS, Chao YJ, Wang DL. Cyclic strain-induced reactive oxygen species involved in ICAM-1 gene induction in endothelial cells. Hypertension 31(1):125-30, 1998.
120. Cheng JJ, Wung BS, Chao YJ, Wang DL. Sequential activation of protein kinase C (PKC)- and PKC- contributes to sustained Raf/ERK1/2 activation in endothelial cells under mechanical strain. J Biol Chem 276(33):31368-31375, 2001.
121. Coen P, Cummins P, Birney Y, Devery R, Cahill P. Modulation of nitric oxide and 6-keto-prostaglandin F(1) production in bovine aortic endothelial cells by conjugated linoleic acid. Endothelium 11(3-4):211-20, 2004.
122. Cohen CR, Mills I, Du W, Kamal K, Sumpio BE. Activation of the adenylyl cyclase/cyclic AMP/protein kinase A pathway in endothelial cells exposed to cyclic strain. Exp Cell Res 231(1):184-189, 1997.
123. Cummins PM, Cotter EJ, Cahill PA. Hemodynamic regulation of metallopeptidases within the vasculature. Protein Pept Lett 11(5):433-442, 2004.
124. Cummins PM, von Offenberg Sweeney N, Killeen MT, Birney YA, Redmond EM, Cahill PA. Cyclic strain-mediated matrix metalloproteinase regulation within the vascular endothelium: a force to be reckoned with. Am J Physiol Heart Circ Physiol 292:H28–H42, 2007.
125. Dekker RJ, van Thienen JV, Rohlena J, de Jager SC, Elderkamp YW, Seppen J, de Vries CJ, Biessen EA, van Berkel TJ, Pannekoek H, Horrevoets AJ. Endothelial KLF2 links local arterial shear stress levels to the expression of vascular tone-regulating genes. Am J Pathol 167(2):609-618, 2005.
126. Dong R, Zhang K, Wang YL, Zhang F, Cao J, Zheng JB, Zhang HJ. MiR-551b-5p contributes to pathogenesis of vein graft failure via upregulating early growth response-1 expression. Chin Med J (Engl) 130(13):1578-1585, 2017.
127. Du W, Mills I, Sumpio BE. Cyclic strain causes heterogeneous induction of transcription factors, AP-1, CRE binding protein and NF-B, in endothelial cells: species and vascular bed diversity. Journal of Biomechanics 28(12):1485-149, 1995.
128. Evans L, Frenkel L, Brophy CM, Rosales O, Sudhaker CB, Li G, Du W, Sumpio BE. Activation of diacylglycerol in cultured endothelial cells exposed to cyclic strain. Am J Physiol 272(2 Pt 1):C650-C656, 1997.
FLEXCELL® INTERNATIONAL CORPORATION
13
129. Fisslthaler B, Boengler K, Fleming I, Schaper W, Busse R, Deindl E. Identification of a cis-element regulating transcriptional activity in response to fluid shear stress in bovine aortic endothelial cells. Endothelium 10(4-5):267-75, 2003.
130. Fisslthaler B, Popp R, Michaelis UR, Kiss L, Fleming I, Busse R. Cyclic stretch enhances the expression and activity of coronary endothelium-derived hyperpolarizing factor synthase. Hypertension 38(6):1427-1432, 2001.
131. Freese C, Anspach L, Deller RC, Richards SJ, Gibson MI, Kirkpatrick CJ, Unger RE. Gold nanoparticle interactions with endothelial cells cultured under physiological conditions. Biomater Sci 5(4):707-717, 2017.
132. Fujioka K, Azuma N, Kito H, Gahtan V, Esato K, Sumpio BE. Role of caveolin in hemodynamic force-mediated endothelial changes. J Surg Res 92(1):7-10, 2000.
133. Gawlak G, Tian Y, O'Donnell JJ 3rd, Tian X, Birukova AA, Birukov KG. Paxillin mediates stretch-induced Rho signaling and endothelial permeability via assembly of paxillin-p42/44MAPK-GEF-H1 complex. FASEB J 28(7):3249-60, 2014.
134. Ghosh K, Thodeti CK, Dudley AC, Mammoto A, Klagsbrun M, Ingber DE. Tumor-derived endothelial cells exhibit aberrant Rho-mediated mechanosensing and abnormal angiogenesis in vitro. Proc Natl Acad Sci U S A 105(32):11305-11310, 2008.
135. Goettsch C, Goettsch W, Arsov A, Hofbauer LC, Bornstein SR, Morawietz H. Long-term cyclic strain downregulates endothelial Nox4. Antioxid Redox Signal 11(10):2385-2397, 2009.
136. Grigoryev DN, Ma SF, Irizarry RA, Ye SQ, Quackenbush J, Garcia JG. Orthologous gene-expression profiling in multi-species models: search for candidate genes. Genome Biol 5(5):R34, 2004.
137. Haga M, Chen A, Gortler D, Dardik A, Sumpio BE. Shear stress and cyclic strain may suppress apoptosis in endothelial cells by different pathways. Endothelium 10(3):149-57, 2003.
138. Hishikawa K, Luscher TF. Pulsatile stretch stimulates superoxide production in human aortic endothelial cells. Circulation 96(10):3610-3616, 1997.
139. Hoshino Y, Nishimura K, Sumpio BE. Phosphatase PTEN is inactivated in bovine aortic endothelial cells exposed to cyclic strain. J Cell Biochem 100(2):515-526, 2007.
140. Howard AB, Alexander RW, Nerem RM, Griendling KK, Taylor WR. Cyclic strain induces an oxidative stress in endothelial cells. Am J Physiol Cell Physiol 272(2):C421-C427, 1997.
141. Hu J, Liu Y. Cyclic strain enhances cellular uptake of nanoparticles. Journal of Nanomaterials 2015:953584, 2015.
142. Iba T, Mills I, Sumpio BE. Intracellular cyclic AMP levels in endothelial cells subjected to cyclic strain in vitro. J Surg Res 52(6):625-630, 1992.
143. Iba T, Shin T, Sonoda T, Rosales O, Sumpio BE. Stimulation of endothelial secretion of tissue-type plasminogen activator by repetitive stretch. J Surg Res 50(5):457-460, 1991.
144. Iba T, Sumpio BE. Morphological response of human endothelial cells subjected to cyclic strain in vitro. Microvasc Res 42(3):245-254, 1991.
145. Ikeda M, Kito H, Sumpio BE. Phosphatidylinositol-3 kinase dependent MAP kinase activation via p21ras in endothelial cells exposed to cyclic strain. Biochem Biophys Res Commun 257(3):668-671, 1999.
146. Ikeda M, Takei T, Mills I, Kito H, Sumpio BE. Extracellular signal-regulated kinases 1 and 2 activation in endothelial cells exposed to cyclic strain. Am J Physiol Heart Circ Physiol 276:H614-H622, 1999.
147. Ikeda M, Takei T, Mills I, Sumpio BE. Calcium-independent activation of extracellular signal-regulated kinases 1 and 2 by cyclic strain. Biochem Biophys Res Commun 247(2):462-465, 1998.
148. Jiang J, Qi YX, Zhang P, Gu WT, Yan ZQ, Shen BR, Yao QP, Kong H, Chien S, Jiang ZL. Involvement of Rab28 in NF-B nuclear transport in endothelial cells. PLoS One 8(2):e56076, 2013.
149. Jiang Y, Wang Y, Tang G. Cyclic tensile strain promotes the osteogenic differentiation of a bone marrow stromal cell and vascular endothelial cell co-culture system. Arch Biochem Biophys 607:37-43, 2016.
150. Juan SH, Chen JJ, Chen CH, Lin H, Cheng CF, Liu JC, Hsieh MH, Chen YL, Chao HH, Chen TH, Chan P, Cheng TH. 17-estradiol inhibits cyclic strain-induced endothelin-1 gene expression within vascular endothelial cells. Am J Physiol Heart Circ Physiol 287(3):H1254-H1261, 2004.
151. Kim JI, Cordova AC, Hirayama Y, Madri JA, Sumpio BE. Differential effects of shear stress and cyclic strain on Sp1 phosphorylation by protein kinase C  modulates membrane type 1-matrix metalloproteinase in endothelial cells. Endothelium 15(1):33-42, 2008.
152. Kito H, Yokoyama C, Inoue H, Tanabe T, Nakajima N, Sumpio BE. Cyclooxygenase expression in bovine aortic endothelial cells exposed to cyclic strain. Endothelium 6(2):107-112, 1998.
FLEXCELL® INTERNATIONAL CORPORATION
14
153. Kobayashi K, Tanaka M, Nebuya S, Kokubo K, Fukuoka Y, Harada Y, Kobayashi H, Noshiro M, Inaoka H. Temporal change in IL-6 mRNA and protein expression produced by cyclic stretching of human pulmonary artery endothelial cells. Int J Mol Med 30(3):509-13, 2012.
154. Korff T, Aufgebauer K, Hecker M. Cyclic stretch controls the expression of CD40 in endothelial cells by changing their transforming growth factor-1 response. Circulation 116(20):2288-2297, 2007.
155. Korff T, Ernst E, Nobiling R, Feldner A, Reiss Y, Plate KH, Fiedler U, Augustin HG, Hecker M. Angiopoietin-1 mediates inhibition of hypertension-induced release of angiopoietin-2 from endothelial cells. Cardiovasc Res 94(3):510-8, 2012.
156. Kou B, Zhang J, Singer DR. Effects of cyclic strain on endothelial cell apoptosis and tubulogenesis are dependent on ROS production via NAD(P)H subunit p22phox. Microvasc Res 77(2):125-133, 2009.
157. Kuk H, Arnold C, Meyer R, Hecker M, Korff T. Magnolol inhibits venous remodeling in mice. Sci Rep 7(1):17820, 2017. doi: 10.1038/s41598-017-17910-0.
158. Lauth M, Cattaruzza M, Hecker M. ACE inhibitor and AT1 antagonist blockade of deformation-induced gene expression in the rabbit jugular vein through B2 receptor activation. Arterioscler Thromb Vasc Biol 21(1):61-6, 2001.
159. Lauth M, Wagner AH, Cattaruzza M, Orzechowski HD, Paul M, Hecker M. Transcriptional control of deformation-induced preproendothelin-1 gene expression in endothelial cells. J Mol Med 78(8):441-450, 2000.
160. Lee T, Kim SJ, Sumpio BE. Role of PP2A in the regulation of p38 MAPK activation in bovine aortic endothelial cells exposed to cyclic strain. J Cell Physiol 194(3):349-355, 2003.
161. Li W, Sumpio BE. Strain-induced vascular endothelial cell proliferation requires PI3K-dependent mTOR-4E-BP1 signal pathway. Am J Physiol Heart Circ Physiol 288(4):H1591-1597, 2005.
162. Loperena R, Chen W, Kirabo A, Harrison DG. Hypertensive mechanical stretch: A model for monocyte-derived dendritic cell differentiation [abstract]. The FASEB Journal 30(1):723.4, 2016.
163. Mai J, Hu Q, Xie Y, Su S, Qiu Q, Yuan W, Yang Y, Song E, Chen Y, Wang J. Dyssynchronous pacing triggers endothelial-mesenchymal transition through heterogeneity of mechanical stretch in a canine model. Circ J 79(1):201-9, 2015.
164. Martin FA, McLoughlin A, Rochfort KD, Davenport C, Murphy RP, Cummins PM. Regulation of thrombomodulin expression and release in human aortic endothelial cells by cyclic strain. PLoS One 9(9):e108254, 2014.
165. Mascarenhas JB, Tchourbanov AY, Fan H, Danilov SM, Wang T, Garcia JG. Mechanical stress and single nucleotide variants regulate alternative splicing of the MYLK gene. Am J Respir Cell Mol Biol 56(1):29-37, 2017. doi: 10.1165/rcmb.2016-0053OC.
166. McIntosh CT, Warnock JN. Side-specific characterization of aortic valve endothelial cell adhesion molecules under cyclic strain. The Journal of Heart Valve Disease 22:631-639, 2013.
167. Metzler SA, Pregonero CA, Butcher JT, Burgess SC, Warnock JN. Cyclic strain regulates pro-inflammatory protein expression in porcine aortic valve endothelial cells. J Heart Valve Dis 17(5):571-577, 2008.
168. Moldobaeva A, Jenkins J, Wagner E. Effects of distension on airway inflammation and venular P-selectin expression. Am J Physiol Lung Cell Mol Physiol 295(5):L941-L948, 2008.
169. Morrow D, Cullen JP, Cahill PA, Redmond EM. Cyclic strain regulates the Notch/CBF-1 signaling pathway in endothelial cells: role in angiogenic activity. Arterioscler Thromb Vasc Biol 27:1289-1296, 2007.
170. Murata K, Mills I, Sumpio BE. Protein phosphatase 2A in stretch-induced endothelial cell proliferation. J Cell Biochem 63(3):311-319, 1996.
171. Neto F, Klaus-Bergmann A, Ong YT, Alt S, Vion AC, Szymborska A, Carvalho JR, Hollfinger I, Bartels-Klein E, Franco CA, Potente M, Gerhardt H. YAP and TAZ regulate adherens junction dynamics and endothelial cell distribution during vascular development. Elife 2018 Feb 5;7. pii: e31037. doi: 10.7554/eLife.31037. [Epub ahead of print]
172. Nishimura K, Li W, Hoshino Y, Kadohama T, Asada H, Ohgi S, Sumpio BE. Role of AKT in cyclic strain-induced endothelial cell proliferation and survival. Am J Physiol Cell Physiol 290(3):C812-C821, 2006.
173. Okada M, Matsumori A, Ono K, Furukawa Y, Shioi T, Iwasaki A, Matsushima K, Sasayama S. Cyclic stretch upregulates production of interleukin-8 and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in human endothelial cells. Arterioscler Thromb Vasc Biol 18(6):894-901, 1998.
174. Pikkarainen S, Tokola H, Kerkela R, Ilves M, Makinen M, Orzechowski HD, Paul M, Vuolteenaho O, Ruskoaho H. Inverse regulation of preproendothelin-1 and endothelin-converting enzyme-1 genes in cardiac cells by mechanical load. Am J Physiol Regul Integr Comp Physiol 290(6):R1639-R1645, 2006.
FLEXCELL® INTERNATIONAL CORPORATION
15
175. Rakugi H, Yu H, Kamitani A, Nakamura Y, Ohishi M, Kamide K, Nakata Y, Takami S, Higaki J, Ogihara T. Links between hypertension and myocardial infarction. American Heart Journal 132(1 Pt 2 Su):213-221, 1996.
176. Regnault V, Perret-Guillaume C, Kearney-Schwartz A, Max JP, Labat C, Louis H, Wahl D, Pannier B, Lecompte T, Weryha G, Challande P, Safar ME, Benetos A, Lacolley P. Tissue factor pathway inhibitor: a new link among arterial stiffness, pulse pressure, and coagulation in postmenopausal women. Arterioscler Thromb Vasc Biol 31(5):1226-1232, 2011.
177. Rosales OR, Isales CM, Barrett PQ, Brophy C, Sumpio BE. Exposure of endothelial cells to cyclic strain induces elevations of cytosolic Ca2+ concentration through mobilization of intracellular and extracellular pools. Biochem J 326(Pt 2):385-92, 1997.
178. Rosales OR, Sumpio BE. Changes in cyclic strain increase inositol trisphosphate and diacylglycerol in endothelial cells. Am J Physiol Cell Physiol 262(4):C956-C962, 1992.
179. Schneider SW, Yano Y, Sumpio BE, Jena BP, Geibel JP, Gekle M, Oberleithner H. Rapid aldosterone-induced cell volume increase of endothelial cells measured by the atomic force microscope. Cell Biol Int 21(11):759-768, 1997.
180. Segurola RJ Jr, Oluwole B, Mills I, Yokoyama C, Tanabe T, Kito H, Nakajima N, Sumpio BE. Cyclic strain is a weak inducer of prostacyclin synthase expression in bovine aortic endothelial cells. J Surg Res 69(1):135-138, 1997.
181. Sheikh AQ, Kuesel C, Taghian T, Hurley JR, Huang W, Wang Y, Hinton RB, Narmoneva DA. Angiogenic microenvironment augments impaired endothelial responses under diabetic conditions. Am J Physiol Cell Physiol 306(8):C768-78, 2014.
182. Steadman E, Meza D, Rubenstein DA, Yin W. Endothelial cell mechanical responses are dependent on both fluid shear stress and tensile strain. The FASEB Journal 31(1 Supplement), 689-16, 2017.
183. Sumpio BE, Banes AJ, Buckley M, Johnson G Jr. Alterations in aortic endothelial cell morphology and cytoskeletal protein synthesis during cyclic tensional deformation. J Vasc Surg 7(1):130-138, 1988.
184. Sumpio BE, Banes AJ, Levin LG, Johnson G Jr. Mechanical stress stimulates aortic endothelial cells to proliferate. J Vasc Surg 6(3):252-256, 1987.
185. Sumpio BE, Banes AJ, Link GW, Iba T. Modulation of endothelial cell phenotype by cyclic stretch: inhibition of collagen production. J Surg Res 48(5):415-420, 1990.
186. Sumpio BE, Banes AJ. Prostacyclin synthetic activity in cultured aortic endothelial cells undergoing cyclic mechanical deformation. Surgery 104(2):383-389, 1988.
187. Sumpio BE, Chang R, Xu WJ, Wang XJ, Du W. Regulation of tPA in endothelial cells exposed to cyclic strain: role of CRE, AP-2, and SSRE binding sites. Am J Physiol Cell Physiol 273:C1441-C1448, 1997.
188. Sumpio BE, Du W, Galagher G, Wang X, Khachigian LM, Collins T, Gimbrone MA Jr, Resnick N. Regulation of PDGF-B in endothelial cells exposed to cyclic strain. Arterioscler Thromb Vasc Biol 18(3):349-355, 1998.
189. Sun X, Elangovan VR, Mapes B, Camp SM, Sammani S, Saadat L, Ceco E, Ma SF, Flores C, MacDougall MS, Quijada H, Liu B, Kempf CL, Wang T, Chiang ET, Garcia JG. The NAMPT promoter is regulated by mechanical stress, signal transducer and activator of transcription 5, and acute respiratory distress syndrome-associated genetic variants. Am J Respir Cell Mol Biol 51(5):660-7, 2014.
190. Thodeti CK, Matthews B, Ravi A, Mammoto A, Ghosh K, Bracha AL, Ingber DE. TRPV4 channels mediate cyclic strain-induced endothelial cell reorientation through integrin-to-integrin signaling. Circ Res 104(9):1123-1130, 2009.
191. Tomanek RJ, Zheng W. Role of growth factors in coronary morphogenesis. Tex Heart Inst J 29(4):250-254, 2002.
192. Ulfhammer E, Ridderstrale W, Andersson M, Karlsson L, Hrafnkelsdottir T, Jern S. Prolonged cyclic strain impairs the fibrinolytic system in cultured vascular endothelial cells. J Hypertens 23(8):1551-1557, 2005.
193. Upchurch GR Jr, Loscalzo J, Banes AJ. Changes in the amplitude of cyclic load biphasically modulate endothelial cell DNA synthesis and division. Vasc Med 2(1):19-24, 1997.
194. van Wamel AJ, Ruwhof C, van der Valk-Kokshoom LE, Schrier PI, van der Laarse A. The role of angiotensin II, endothelin-1 and transforming growth factor- as autocrine/paracrine mediators of stretch-induced cardiomyocyte hypertrophy. Mol Cell Biochem 218(1-2):113-124, 2001.
195. van Wamel AJ, Ruwhof C, van der Valk-Kokshoorn LJ, Schrier PI, van der Laarse A. Stretch-induced paracrine hypertrophic stimuli increase TGF-1 expression in cardiomyocytes. Mol Cell Biochem 236(1-2):147-153, 2002.
FLEXCELL® INTERNATIONAL CORPORATION
16
196. Vion AC, Birukova AA, Boulanger CM, Birukov KG. Mechanical forces stimulate endothelial microparticle generation via caspase-dependent apoptosis-independent mechanism. Pulm Circ 3(1):95-9, 2013.
197. Vollmer T, Hinse D, Kleesiek K, Dreier J. Interactions between endocarditis-derived Streptococcus gallolyticus subsp. Gallolyticus isolates and human endothelial cells. BMC Microbiology 10:78, 2010.
198. von Offenberg Sweeney N, Cummins PM, Birney YA, Cullen JP, Redmond EM, Cahill PA. Cyclic strain-mediated regulation of endothelial matrix metalloproteinase-2 expression and activity. Cardiovascular Research 63(4):625-634, 2004.
199. von Offenberg Sweeney N, Cummins PM, Birney YA, Redmond EM, Cahill PA. Cyclic strain-induced endothelial MMP-2: role in vascular smooth muscle cell migration. Biochemical and Biophysical Research Communications 320:325–333, 2004.
200. von Offenberg Sweeney, Cummins PM, Cotter EJ, Fitzpatrick PA, Birney YA, Redmond EM, Cahill PA. Cyclic strain-mediated regulation of vascular endothelial cell migration and tube formation. Biochemical and Biophysical Research Communications 329:573–582, 2005.
201. Wang C, Jiao C, Hanlon HD, Zheng W, Tomanek RJ, Schatteman GC. Mechanical, cellular, and molecular factors interact to modulate circulating endothelial cell progenitors. Am J Physiol Heart Circ Physiol 286(5):H1985-H1993, 2004.
202. Wang DL, Wung BS, Peng YC, Wang JJ. Mechanical strain increases endothelin-1 gene expression via protein kinase C pathway in human endothelial cells. J Cell Physiol 163(2):400-406, 1995.
203. Wang DL, Wung BS, Shyy YJ, Lin CF, Chao YJ, Usami S, Chien S. Mechanical strain induces monocyte chemotactic protein-1 gene expression in endothelial cells. Effects of mechanical strain on monocyte adhesion to endothelial cells. Circ Res 77(2):294-302, 1995.
204. Wang L, Bao H, Wang KX, Zhang P, Yao QP, Chen XH, Huang K, Qi YX, Jiang ZL. Secreted miR-27a induced by cyclic stretch modulates the proliferation of endothelial cells in hypertension via GRK6. Sci Rep 7:41058, 2017.
205. Widmann MD, Letsou GV, Phan S, Baldwin JC, Sumpio BE. Isolation and characterization of rabbit cardiac endothelial cells: response to cyclic strain and growth factors in vitro. Journal of Surgical Research 53(4):331-334, 1992.
206. Wilson CJ, Kasper G, Schütz MA, Duda GN. Cyclic strain disrupts endothelial network formation on Matrigel. Microvasc Res 78(3):358-63, 2009.
207. Woodell JE, LaBerge M, Langan EM 3rd, Hilderman RH. In vitro strain-induced endothelial cell dysfunction determined by DNA synthesis. Proc Inst Mech Eng [H] 217(1):13-20, 2003.
208. Woodell JE, LaBerge M, Langan EM 3rd, Hilderman RH. P1,P4-diadenosine 5'-tetraphosphate induced DNA synthesis in mechanically injured cultured endothelial cells. Proc Inst Mech Eng [H] 217(1):21-26, 2003.
209. Wung BS, Cheng JJ, Chao YJ, Hsieh HJ, Wang DL. Modulation of Ras/Raf/extracellular signal-regulated kinase pathway by reactive oxygen species is involved in cyclic strain-induced early growth response-1 gene expression in endothelial cells. Circ Res 84(7):804-812, 1999.
210. Wung BS, Cheng JJ, Chao YJ, Lin J, Shyy YJ, Wang DL. Cyclical strain increases monocyte chemotactic protein-1 secretion in human endothelial cells. Am J Physiol Heart Circ Physiol 270(4):H1462-H1468, 1996.
211. Wung BS, Cheng JJ, Hsieh HJ, Shyy YJ, Wang DL. Cyclic strain-induced monocyte chemotactic protein-1 gene expression in endothelial cells involves reactive oxygen species activation of activator protein 1. Circ Res 81(1):1-7, 1997.
212. Wung BS, Cheng JJ, Shyue SK, Wang DL. NO modulates monocyte chemotactic protein-1 expression in endothelial cells under cyclic strain. Arterioscler Thromb Vasc Biol 21(12):1941-1947, 2001.
213. Yamaguchi S, Yamaguchi M, Yatsuyanagi E, Yun SS, Nakajima N, Madri JA, Sumpio BE. Cyclic strain stimulates early growth response gene product 1-mediated expression of membrane type 1 matrix metalloproteinase in endothelium. Lab Invest 82(7):949-956, 2002.
214. Yano Y, Geibel J, Sumpio BE. Cyclic strain induces reorganization of integrin 51 and 21 in human umbilical vein endothelial cells. J Cell Biochem 64(3):505-513, 1997.
215. Yano Y, Geibel J, Sumpio BE. Tyrosine phosphorylation of pp125FAK and paxillin in aortic endothelial cells induced by mechanical strain. Am J Physiol Cell Physiol 271:C635-C649, 1996.
216. Yano Y, Saito Y, Narumiya S, Sumpio BE. Involvement of rho p21 in cyclic strain-induced tyrosine phosphorylation of focal adhesion kinase (pp125FAK), morphological changes and migration of endothelial cells. Biochem Biophys Res Commun 224(2):508-515, 1996.
FLEXCELL® INTERNATIONAL CORPORATION
17
217. Zheng W, Christensen LP, Tomanek RJ. Stretch induces upregulation of key tyrosine kinase receptors in microvascular endothelial cells. Am J Physiol Heart Circ Physiol 287(6):H2739-H2745, 2004.
218. Zheng W, Seftor EA, Meininger CJ, Hendrix MJ, Tomanek RJ. Mechanisms of coronary angiogenesis in response to stretch: role of VEGF and TGF-. Am J Physiol Heart Circ Physiol 280(2):H909-H917, 2001.
219. Zheng W, Christensen LP, Tomanek RJ. Differential effects of cyclic and static stretch on coronary microvascular endothelial cell receptors and vasculogenic/angiogenic responses. Am J Physiol Heart Circ Physiol 295:H794–H800, 2008.
CARDIOVASCULAR SMOOTH MUSCLE CELLS
220. Allison DA, Wight TN, Ripp NJ, Braun KR, Grande-Allen KJ. Endogenous overexpression of hyaluronan synthases within dynamically cultured collagen gels: implications for vascular and valvular disease. Biomaterials 29:2969-2976, 2008.
221. Arnold C, Demirel E, Feldner A, Genové G, Zhang H, Sticht C, Wieland T, Hecker M, Heximer S, Korff T. Hypertension-evoked RhoA activity in vascular smooth muscle cells requires RGS5. FASEB J 2018 Jan 5:fj201700384RR. doi: 10.1096/fj.201700384RR. [Epub ahead of print]
222. Arnold C, Feldner A, Pfisterer L, Hödebeck M, Troidl K, Genové G, Wieland T, Hecker M, Korff T. RGS5 promotes arterial growth during arteriogenesis. EMBO Mol Med 6(8):1075-89, 2014.
223. Bai X, Mangum KD, Dee RA, Stouffer GA, Lee CR, Oni-Orisan A, Patterson C, Schisler JC, Viera AJ, Taylor JM, Mack CP. Blood pressure-associated polymorphism controls ARHGAP42 expression via serum response factor DNA binding. J Clin Invest 127(2):670-680, 2017.
224. Birukov KG, Shirinsky VP, Stepanova OV, Tkachuk VA, Hahn AW, Resink TJ, Smirnov VN. Stretch affects phenotype and proliferation of vascular smooth muscle cells. Mol Cell Biochem 144(2):131-139, 1995.
225. Capers Q 4th, Alexander RW, Lou P, De Leon H, Wilcox JN, Ishizaka N, Howard AB, Taylor WR. Monocyte chemoattractant protein-1 expression in aortic tissues of hypertensive rats. Hypertension 30(6):1397-1402, 1997.
226. Cattaruzza M, Berger MM, Ochs M, Fayyazi A, Fuzesi L, Richter J, Hecker M. Deformation-induced endothelin B receptor-mediated smooth muscle cell apoptosis is matrix-dependent. Cell Death Differ 9(2):219-226, 2002.
227. Cattaruzza M, Dimigen C, Ehrenreich H, Hecker M. Stretch-induced endothelin B receptor-mediated apoptosis in vascular smooth muscle cells. FASEB J 14(7):991-998, 2000.
228. Chang H, Shyu KG, Wang BW, Kuan P. Regulation of hypoxia-inducible factor-1 by cyclical mechanical stretch in rat vascular smooth muscle cells. Clin Sci (Lond) 105(4):447-456, 2003.
229. Chapman GB, Durante W, Hellums JD, Schafer AI. Physiological cyclic stretch causes cell cycle arrest in cultured vascular smooth muscle cells. Am J Physiol Heart Circ Physiol 278:H748-H754, 2000.
230. Chen AH, Gortler DS, Kilaru S, Araim O, Frangos SG, Sumpio BE. Cyclic strain activates the pro-survival Akt protein kinase in bovine aortic smooth muscle cells. Surgery 130(2):378-381, 2001.
231. Chen Q, Li W, Quan Z, Sumpio BE. Modulation of vascular smooth muscle cell alignment by cyclic strain is dependent on reactive oxygen species and P38 mitogen-activated protein kinase. J Vasc Surg 37(3):660-668, 2003.
232. Cheng J, Du J. Mechanical stretch simulates proliferation of venous smooth muscle cells through activation of the insulin-like growth factor-1 receptor. Arterioscler Thromb Vasc Biol 27(8):1744-1751, 2007.
233. Cheng J, Zhang J, Merched A, Zhang L, Zhang P, Truong L, Boriek AM, Du J. Mechanical stretch inhibits oxidized low density lipoprotein-induced apoptosis in vascular smooth muscle cells by up-regulating integrin V3 and stablization of PINCH-1. J Biol Chem 282(47):34268-34275, 2007.
234. Cheng WP, Hung HF, Wang BW, Shyu KG. The molecular regulation of GADD153 in apoptosis of cultured vascular smooth muscle cells by cyclic mechanical stretch. Cardiovascular Research 77:551–559, 2008.
235. Cheng WP, Wang BW, Chen SC, Chang H, Shyu KG. Mechanical stretch induces the apoptosis regulator PUMA in vascular smooth muscle cells. Cardiovasc Res 93(1):181-9, 2012.
236. Chiu CZ, Wang BW, Shyu KG. Effects of cyclic stretch on the molecular regulation of myocardin in rat aortic vascular smooth muscle cells. J Biomed Sci 20:50, 2013.
237. Clements ML, Banes AJ, Faber JE. Effect of mechanical loading on vascular 1D- and 1B-adrenergic receptor expression. Hypertension 29(5):1156-1164, 1997.
238. Clements ML, Faber JE. Mechanical load opposes angiotensin-mediated decrease in vascular 1-adrenoceptors. Hypertension 29(5):1165-1172, 1997.
FLEXCELL® INTERNATIONAL CORPORATION
18
239. Colombo A, Guha S, Mackle JN, Cahill PA, Lally C. Cyclic strain amplitude dictates the growth response of vascular smooth muscle cells in vitro: role in in-stent restenosis and inhibition with a sirolimus drug-eluting stent. Biomech Model Mechanobiol 12(4):671-83, 2013.
240. Cunningham JJ, Linderman JJ, Mooney DJ. Externally applied cyclic strain regulates localization of focal contact components in cultured smooth muscle cells. Ann Biomed Eng 30(7):927-935, 2002.
241. Dangers M, Kiyan J, Grote K, Schieffer B, Haller H, Dumler I. Mechanical stress modulates SOCS-1 expression in human vascular smooth muscle cells. J Vasc Res 47(5):432-440, 2010.
242. Davis MG, Ali S, Leikauf GD, Dorn GW 2nd. Tyrosine kinase inhibition prevents deformation-stimulated vascular smooth muscle growth. Hypertension 24(6):706-713, 1994.
243. Dethlefsen SM, Shepro D, D'Amore PA. Comparison of the effects of mechanical stimulation on venous and arterial smooth muscle cells in vitro. J Vasc Res 33(5):405-413, 1996.
244. de Waard V, Arkenbout EK, Vos M, Mocking AI, Niessen HW, Stooker W, de Mol BA, Quax PH, Bakker EN, VanBavel E, Pannekoek H, de Vries CJ. TR3 nuclear orphan receptor prevents cyclic stretch-induced proliferation of venous smooth muscle cells. Am J Pathol 168:2027–2035, 2006.
245. Dinardo CL, Venturini G, Zhou EH, Watanabe IS, Campos LC, Dariolli R, da Motta-Leal-Filho JM, Carvalho VM, Cardozo KH, Krieger JE, Alencar AM, Pereira AC. Variation of mechanical properties and quantitative proteomics of VSMC along the arterial tree. Am J Physiol Heart Circ Physiol 306(4):H505-16, 2014.
246. Eschrich J, Meyer R, Kuk H, Wagner AH, Noppeney T, Debus S, Hecker M, Korff T. Varicose remodeling of veins is suppressed by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. J Am Heart Assoc 5(2), pii: e002405, 2016.
247. Faber JE, Yang N, Xin X. Expression of -adrenoceptor subtypes by smooth muscle cells and adventitial fibroblasts in rat aorta and in cell culture. J Pharmacol Exp Ther 298(2):441-452, 2001.
248. Ghosh S, Kollar B, Nahar T, Suresh Babu S, Wojtowicz A, Sticht C, Gretz N, Wagner AH, Korff T, Hecker M. Loss of the mechanotransducer zyxin promotes a synthetic phenotype of vascular smooth muscle cells. J Am Heart Assoc 4(6):e001712, 2015.
249. Granata A, Serrano F, Bernard WG, McNamara M, Low L, Sastry P, Sinha S. An iPSC-derived vascular model of Marfan syndrome identifies key mediators of smooth muscle cell death. Nat Genet 49(1):97-109, 2017. doi: 10.1038/ng.3723. Epub 2016 Nov 28.
250. Grote K, Bavendiek U, Grothusen C, Flach I, Hilfiker-Kleiner D, Drexler H, Schieffer B. Stretch-inducible expression of the angiogenic factor CCN1 in vascular smooth muscle cells is mediated by Egr-1. J Biol Chem 279(53):55675-55681, 2004.
251. Grote K, Flach I, Luchtefeld M, Akin E, Holland SM, Drexler H, Schieffer B. Mechanical stretch enhances mRNA expression and proenzyme release of matrix metalloproteinase-2 (MMP-2) via NAD(P)H oxidase-derived reactive oxygen species. Circ Res 92(11):e80-86, 2003.
252. Hamada K, Takuwa N, Yokoyama K, Takuwa Y. Stretch activates Jun N-terminal kinase/stress-activated protein kinase in vascular smooth muscle cells through mechanisms involving autocrine ATP stimulation of purinoceptors. J Biol Chem 273(11):6334-6340, 1998.
253. Han O, Takei T, Basson M, Sumpio BE. Translocation of PKC isoforms in bovine aortic smooth muscle cells exposed to strain. J Cell Biochem 80(3):367-372, 2001.
254. Hipper A, Isenberg G. Cyclic mechanical strain decreases the DNA synthesis of vascular smooth muscle cells. Pflugers Arch 440(1):19-27, 2000.
255. Hishikawa K, Oemar BS, Yang Z, Luscher TF. Pulsatile stretch stimulates superoxide production and activates nuclear factor-B in human coronary smooth muscle. Circ Res 81(5):797-803, 1997.
256. Hitomi H, Fukui T, Moriwaki K, Matsubara K, Sun GP, Rahman M, Nishiyama A, Kiyomoto H, Kimura S, Ohmori K, Abe Y, Kohno M. Synergistic effect of mechanical stretch and angiotensin II on superoxide production via NADPH oxidase in vascular smooth muscle cells. J Hypertens 24(6):1097-1104, 2006.
257. Hödebeck M, Scherer C, Wagner AH, Hecker M, Korff T. TonEBP/NFAT5 regulates ACTBL2 expression in biomechanically activated vascular smooth muscle cells. Front Physiol 5:467, 2014.
258. Hoffmann SE, Kuriakose M, Songu-Mize E. Stretch-induced downregulation of TRPC4 does not decrease capacitative calcium entry in vascular smooth muscle cells [abstract]. Hypertension 46:P80, 2005.
259. Hoffmann SE, Kuriakose M, Songu-Mize E. Stretch-induced TRPC4 downregulation in RASM cells may be due to changes in intracellular calcium [abstract]. FASEB J 20:699.17, 2006.
260. Howard AB, Alexander RW, Nerem RM, Griendling KK, Taylor WR. Cyclic strain induces an oxidative stress in endothelial cells. Am J Physiol Cell Physiol 272(2):C421-C427, 1997.
FLEXCELL® INTERNATIONAL CORPORATION
19
261. Hu B, Song JT, Qu HY, Bi CL, Huang XZ, Liu XX, Zhang M. Mechanical stretch suppresses microRNA-145 expression by activating extracellular signal-regulated kinase 1/2 and upregulating angiotensin-converting enzyme to alter vascular smooth muscle cell phenotype. PLoS One 9(5):e96338, 2014.
262. Hu Y, Bock G, Wick G, Xu Q. Activation of PDGF receptor  in vascular smooth muscle cells by mechanical stress. FASEB J 12(12):1135-1142, 1998.
263. Huang K, Bao H, Yan ZQ, Wang L, Zhang P, Yao QP, Shi Q, Chen XH, Wang KX, Shen BR, Qi YX, Jiang ZL. MicroRNA-33 protects against neointimal hyperplasia induced by arterial mechanical stretch in the grafted vein. Cardiovasc Res 113(5):488-497, 2017.
264. Iwasaki H, Eguchi S, Ueno H, Marumo F, Hirata Y. Mechanical stretch stimulates growth of vascular smooth muscle cells via epidermal growth factor receptor. Am J Physiol Heart Circ Physiol 278(2):H521-H529, 2000.
265. Iwasaki H, Yoshimoto T, Sugiyama T, Hirata Y. Activation of cell adhesion kinase  by mechanical stretch in vascular smooth muscle cells. Endocrinology 144(6):2304-2310, 2003.
266. Jia LX, Zhang WM, Li TT, Liu Y, Piao CM, Ma YC, Lu Y, Wang Y, Liu TT, Qi YF, Du J. ER stress dependent microparticles derived from smooth muscle cells promote endothelial dysfunction during thoracic aortic aneurysm and dissection. Clin Sci (Lond) 131(12):1287-1299, 2017.
267. Jia LX, Zhang WM, Zhang HJ, Li TT, Wang YL, Qin YW, Gu H, Du J. Mechanical stretch-induced endoplasmic reticulum stress, apoptosis and inflammation contribute to thoracic aortic aneurysm and dissection. J Pathol 236(3):373-83, 2015.
268. Jiang J, Qi YX, Zhang P, Gu WT, Yan ZQ, Shen BR, Yao QP, Kong H, Chien S, Jiang ZL. Involvement of Rab28 in NF-B nuclear transport in endothelial cells. PLoS One 8(2):e56076, 2013.
269. Jiang MJ, Yu YJ, Chen YL, Lee YM, Hung LS. Cyclic strain stimulates monocyte chemotactic protein-1 mRNA expression in smooth muscle cells. J Cell Biochem 76(2):303-310, 2000.
270. Jiang WJ, Ren WH, Liu XJ, Liu Y, Wu FJ, Sun LZ, Lan F, Du J, Zhang HJ. Disruption of mechanical stress in extracellular matrix is related to Stanford type A aortic dissection through down-regulation of Yes-associated protein. Aging (Albany NY) 8(9):1923-1939, 2016.
271. Kakisis JD, Pradhan S, Cordova A, Liapis CD, Sumpio BE. The role of STAT-3 in the mediation of smooth muscle cell response to cyclic strain. Int J Biochem Cell Biol 37(7):1396-1406, 2005.
272. Kawabe J, Okumura S, Lee MC, Sadoshima J, Ishikawa Y. Translocation of caveolin regulates stretch-induced ERK activity in vascular smooth muscle cells. Am J Physiol Heart Circ Physiol 286(5):H1845-1852, 2004.
273. Kim BS, Nikolovski J, Bonadio J, Mooney DJ. Cyclic mechanical strain regulates the development of engineered smooth muscle tissue. Nat Biotech 17(10):979-983, 1999.
274. Kogata N, Tribe RM, Fässler R, Way M, Adams RH. Integrin-linked kinase controls vascular wall formation by negatively regulating Rho/ROCK-mediated vascular smooth muscle cell contraction. Genes Dev 23(19):2278-2283, 2009.
275. Kona S, Chellamuthu P, Xu H, Hills SR, Nguyen KT. Effects of cyclic strain and growth factors on vascular smooth muscle cell responses. Open Biomed Eng J 3:28-38, 2009.
276. Kozai T, Eto M, Yang Z, Shimokawa H, Luscher TF. Statins prevent pulsatile stretch-induced proliferation of human saphenous vein smooth muscle cells via inhibition of Rho/Rho-kinase pathway. Cardiovasc Res 68(3):475-482, 2005.
277. Kurpinski K, Park J, Thakar RG, Li S. Regulation of vascular smooth muscle cells and mesenchymal stem cells by mechanical strain. Mol Cell Biomech 3(1):21-34, 2006.
278. Lee EL, Bendre HH, Kalmykov A, Wong JY. Surface modification of uniaxial cyclic strain cell culture platform with temperature-responsive polymer for cell sheet detachment. J Mater Chem B Mater Biol Med 3(40):7899-7902, 2015.
279. Li C, Hu Y, Mayr M, Xu Q. Cyclic strain stress-induced mitogen-activated protein kinase (MAPK) phosphatase 1 expression in vascular smooth muscle cells is regulated by Ras/Rac-MAPK pathways. J Biol Chem 274(36):25273-25280, 1999.
280. Li C, Hu Y, Sturm G, Wick G, Xu Q. Ras/Rac-Dependent activation of p38 mitogen-activated protein kinases in smooth muscle cells stimulated by cyclic strain stress. Arterioscler Thromb Vasc Biol 20(3):E1-E9, 2000.
281. Li Q, Muragaki Y, Hatamura I, Ueno H, Ooshima A. Stretch-induced collagen synthesis in cultured smooth muscle cells from rabbit aortic media and a possible involvement of angiotensin II and transforming growth factor-. J Vasc Res 35(2):93-103, 1998.
FLEXCELL® INTERNATIONAL CORPORATION
20
282. Li W, Chen Q, Mills I, Sumpio BE. Involvement of S6 kinase and p38 mitogen activated protein kinase pathways in strain-induced alignment and proliferation of bovine aortic smooth muscle cells. J Cell Physiol 195(2):202-209, 2003.
283. Licht AH, Nübel T, Feldner A, Jurisch-Yaksi N, Marcello M, Demicheva E, Hu JH, Hartenstein B, Augustin HG, Hecker M, Angel P, Korff T, Schorpp-Kistner M. Junb regulates arterial contraction capacity, cellular contractility, and motility via its target Myl9 in mice. J Clin Invest 120(7):2307-2318, 2010.
284. Lindsey-Hoffmann SE, Songu-Mize E. Cyclic stretch decreases capacitative calcium entry in vascular smooth muscle cells from resistance and conduit vessels [abstract]. Experimental Biology, 2007.
285. Ling S, Deng G, Ives HE, Chatterjee K, Rubanyi GM, Komesaroff PA, Sudhir K. Estrogen inhibits mechanical strain-induced mitogenesis in human vascular smooth muscle cells via down-regulation of Sp-1. Cardiovascular Research 50(1):108-114, 2001.
286. Liu B, Qu MJ, Qin KR, Li H, Li ZK, Shen BR, Jiang ZL. Role of cyclic strain frequency in regulating the alignment of vascular smooth muscle cells in vitro. Biophys J 94:1497-1507, 2008.
287. Liu G, Hitomi H, Hosomi N, Lei B, Pelisch N, Nakano D, Kiyomoto H, Ma H, Nishiyama A. Mechanical stretch potentiates angiotensin II-induced proliferation in spontaneously hypertensive rat vascular smooth muscle cells. Hypertens Res 33(12):1250-1257, 2010.
288. Liu X, Hymel LJ, Songu-Mize E. Involvement of intracellular Ca2+ and Na+ in stretch-regulated Na+, K+-ATPase  isoform expression in cultured vascular smooth muscle cells [abstract]. FASEB J 11:A263, 1526, 1997.
289. Liu X, Hymel LJ, Songu-Mize E. Mechanosensitivity of Na+, K+-ATPase  subunit expression in aortic smooth muscle cells [abstract]. Biophys J 70:A348, Tu-Pos 497, 1996.
290. Liu X, Hymel LJ, Songu-Mize E. Role of Na+ and Ca2+ in stretch-induced Na+-K+-ATPase -subunit regulation in aortic smooth muscle cells. Am J Physiol Heart Circ Physiol 274:H83–H89, 1998.
291. Liu X, Hymel LJ, Songu-Mize E. Sodium entry through stretch-activated channels mediates upregulation of Na+, K+-ATPase  isoforms in aortic smooth muscle cells [abstract]. Hypertension 30(Part 1):512, P175, 1997.
292. Lundberg MS, Sadhu DN, Grumman VE, Chilian WM, Ramos KS. Actin isoform and 1B-adrenoceptor gene expression in aortic and coronary smooth muscle is influenced by cyclical stretch. In Vitro Cell Dev Biol Anim 31(8):595-600, 1995.
293. Mantella LE, Quan A, Verma S. Variability in vascular smooth muscle cell stretch-induced responses in 2D culture. Vasc Cell 7:7, 2015
294. Mayr M, Li C, Zou Y, Huemer U, Hu Y, Xu Q. Biomechanical stress-induced apoptosis in vein grafts involves p38 mitogen-activated protein kinases. FASEB J 14(2):261-270, 2000.
295. Metzler B, Abia R, Ahmad M, Wernig F, Pachinger O, Hu Y, Xu Q. Activation of heat shock transcription factor 1 in atherosclerosis. Am J Pathol 162(5):1669-1676, 2003.
296. Mills I, Cohen CR, Kamal K, Li G, Shin T, Du W, Sumpio BE. Strain activation of bovine aortic smooth muscle cell proliferation and alignment: study of strain dependency and the role of protein kinase A and C signaling pathways. J Cell Physiol 170(3):228-34, 1997.
297. Mills I, Murata K, Packer CS, Sumpio BE. Cyclic strain stimulates dephosphorylation of the 20kDa regulatory myosin light chain in vascular smooth muscle cells. Biochem Biophys Res Commun 205(1):79-84, 1994. Erratum in: Biochem Biophys Res Commun 207(3):1058, 1995.
298. Mohanty MJ, Li X. Stretch-induced Ca2+ release via an IP3-insensitive Ca2+ channel. Am J Physiol Cell Physiol 283(2):C456-C462, 2002.
299. Molostvov G, Hiemstra TF, Fletcher S, Bland R, Zehnder D. Arterial expression of the calcium-sensing receptor is maintained by physiological pulsation and protects against calcification. PLoS One 10(10):e0138833, 2015.
300. Morawietz H, Ma YH, Vives F, Wilson E, Sukhatme VP, Holtz J, Ives HE. Rapid induction and translocation of Egr-1 in response to mechanical strain in vascular smooth muscle cells. Circ Res 84(6):678-687, 1999.
301. Morrow D, Scheller A, Birney YA, Sweeney C, Guha S, Cummins PM, Murphy R, Walls D, Redmond EM, Cahill PA. Notch-mediated CBF-1/RBP-J-dependent regulation of human vascular smooth muscle cell phenotype in vitro. Am J Physiol Cell Physiol 289(5):C1188-C1196, 2005.
302. Morrow D, Sweeney C, Birney YA, Cummins PM, Walls D, Redmond EM, Cahill PA. Cyclic strain inhibits Notch receptor signaling in vascular smooth muscle cells in vitro. Circ Res 96(5):567-575, 2005.
FLEXCELL® INTERNATIONAL CORPORATION
21
303. Morrow D, Sweeney C, Birney YA, Guha S, Collins N, Cummins PM, Murphy R, Walls D, Redmond EM, Cahill PA. Biomechanical regulation of hedgehog signaling in vascular smooth muscle cells in vitro and in vivo. Am J Physiol Cell Physiol 292(1):C488-C496, 2007.
304. Noda M, Katoh T, Takuwa N, Kumada M, Kurokawa K, Takuwa Y. Synergistic stimulation of parathyroid hormone-related peptide gene expression by mechanical stretch and angiotensin II in rat aortic smooth muscle cells. J Biol Chem 269(27):17911-17917, 1994.
305. Noda M, Takuwa Y, Katoh T, Kurokawa K. Stretch-induced parathyroid hormone-related peptide gene expression: implication in the regulation of myogenic tone. Curr Opin Nephrol Hypertens 4(5):383-387, 1995.
306. Numaguchi K, Eguchi S, Yamakawa T, Motley ED, Inagami T. Mechanotransduction of rat aortic vascular smooth muscle cells requires RhoA and intact actin filaments. Circ Res 85(1):5-11, 1999.
307. O'Callaghan CJ, Williams B. Mechanical strain-induced extracellular matrix production by human vascular smooth muscle cells: role of TGF-1. Hypertension 36(3):319-324, 2000.
308. Pfisterer L, Feldner A, Hecker M, Korff T. Hypertension impairs myocardin function: a novel mechanism facilitating arterial remodelling. Cardiovasc Res 96(1):120-9, 2012.
309. Ping S, Li Y, Liu S, Zhang Z, Wang J, Zhou Y, Liu K, Huang J, Chen D, Wang J, Li C. Simultaneous increases in proliferation and apoptosis of vascular smooth muscle cells accelerate diabetic mouse venous atherosclerosis. PLoS One 10(10):e0141375, 2015.
310. Putnam AJ, Cunningham JJ, Dennis RG, Linderman JJ, Mooney DJ. Microtubule assembly is regulated by externally applied strain in cultured smooth muscle cells. J Cell Sci 111(Pt 22):3379-3387, 1998.
311. Pyle AL, Atkinson JB, Pozzi A, Reese J, Eckes B, Davidson JM, Crimmins DL, Young PP. Regulation of the atheroma-enriched protein, SPRR3, in vascular smooth muscle cells through cyclic strain is dependent on integrin 11/collagen interaction. Am J Pathol 173(5):1577-1588, 2008.
312. Qi YX, Yao QP, Huang K, Shi Q, Zhang P, Wang GL, Han Y, Bao H, Wang L, Li HP, Shen BR, Wang Y, Chien S, Jiang ZL. Nuclear envelope proteins modulate proliferation of vascular smooth muscle cells during cyclic stretch application. Proc Natl Acad Sci U S A 113(19):5293-8, 2016.
313. Qu M, Liu B, Jiang Z. Effect of frequency of cyclic tensile strain on extracellular matrix of rat vascular smooth muscle cells in vitro. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 25(4):826-830, 2008.
314. Qu MJ, Liu B, Qi YX, Jiang ZL. Role of Rac and Rho-GDI  in the frequency-dependent expression of h1-calponin in vascular smooth muscle cells under cyclic mechanical strain. Ann Biomed Eng 36(9):1481-1488, 2008.
315. Qu MJ, Liu B, Wang HQ, Yan ZQ, Shen BR, Jiang ZL. Frequency-dependent phenotype modulation of vascular smooth muscle cells under cyclic mechanical strain. J Vasc Res 44(5):345-353, 2007.
316. Rakugi H, Yu H, Kamitani A, Nakamura Y, Ohishi M, Kamide K, Nakata Y, Takami S, Higaki J, Ogihara T. Links between hypertension and myocardial infarction. American Heart Journal 132(1 Pt 2 Su):213-221, 1996.
317. Regnault V, Perret-Guillaume C, Kearney-Schwartz A, Max JP, Labat C, Louis H, Wahl D, Pannier B, Lecompte T, Weryha G, Challande P, Safar ME, Benetos A, Lacolley P. Tissue factor pathway inhibitor: a new link among arterial stiffness, pulse pressure, and coagulation in postmenopausal women. Arterioscler Thromb Vasc Biol 31(5):1226-1232, 2011.
318. Reusch P, Wagdy H, Reusch R, Wilson E, Ives HE. Mechanical strain increases smooth muscle and decreases nonmuscle myosin expression in rat vascular smooth muscle cells. Circ Res 79(5):1046-1053, 1996.
319. Reyna SV, Ensenat D, Johnson FK, Wang H, Schafer AI, Durante W. Cyclic strain stimulates L-proline transport in vascular smooth muscle cells. American Journal of Hypertension 17(8):712-717, 2004.
320. Richard MN, Deniset JF, Kneesh AL, Blackwood D, Pierce GN. Mechanical stretching stimulates smooth muscle cell growth, nuclear protein import, and nuclear pore expression through mitogen-activated protein kinase activation. J Biol Chem 282(32):23081-23088, 2007.
321. Ruiz-Velasco V, Mayer MB, Hymel LJ. Dihydropyridine-sensitive Ca2+ influx modulated by stretch in A7r5 vascular smooth muscle cells. European Journal of Pharmacology 296(3):327-334, 1996.
322. Schad JF, Meltzer KR, Hicks MR, Beutler DS, Cao TV, Standley PR. Cyclic strain upregulates VEGF and attenuates proliferation of vascular smooth muscle cells. Vasc Cell 3:21, 2011.
323. Scherer C, Pfisterer L, Wagner AH, Hödebeck M, Cattaruzza M, Hecker M, Korff T. Arterial wall stress controls NFAT5 activity in vascular smooth muscle cells. J Am Heart Assoc 3(2):e000626, 2014.
324. Sedding DG, Hermsen J, Seay U, Eickelberg O, Kummer W, Schwencke C, Strasser RH, Tillmanns H, Braun-Dullaeus RC. Caveolin-1 facilitates mechanosensitive protein kinase B (Akt) signaling in vitro and in vivo. Circ Res 96(6):635-642, 2005.
FLEXCELL® INTERNATIONAL CORPORATION
22
325. Sedding DG, Homann M, Seay U, Tillmanns H, Preissner KT, Braun-Dullaeus RC. Calpain counteracts mechanosensitive apoptosis of vascular smooth muscle cells in vitro and in vivo. FASEB J 22(2):579-589, 2008.
326. Sedding DG, Widmer-Teske R, Mueller A, Stieger P, Daniel JM, Gündüz D, Pullamsetti S, Nef H, Moellmann H, Troidl C, Hamm C, Braun-Dullaeus R. Role of the phosphatase PTEN in early vascular remodeling. PLoS One 8(3):e55445, 2013.
327. Seo KW, Lee SJ, Kim YH, Bae JU, Park SY, Bae SS, Kim CD. Mechanical stretch increases MMP-2 production in vascular smooth muscle cells via activation of PDGFR-β/Akt signaling pathway. PLoS One 8(8):e70437, 2013.
328. Sevieux N, Alam J, Songu-Mize E. Effect of cyclic stretch on -subunit mRNA expression of Na+-K+-ATPase in aortic smooth muscle cells. Am J Physiol Cell Physiol 280(6):C1555-C1560, 2001.
329. Sevieux N, Alam J, Songu-Mize E. Effect of cyclic stretch on transcriptional regulation of the  subunits of Na+, K+-ATPase in aortic smooth muscle cells [abstract]. FASEB J 14:A331, 272.5, 2000.
330. Sevieux N, Alam J, Wiltse S, Songu-Mize E. Expression of the  subunit mRNA of Na+, K+-ATPase in response to cyclic stretch in aortic smooth muscle cells [abstract]. FASEB J 13:351.4, 1999.
331. Sevieux N, Ark M, Hornick C, Songu-Mize E. Short-term stretch translocates the -1-subunit of the Na pump to plasma membrane. Cell Biochem Biophys 38(1):23-32, 2003.
332. Shah MR, Wedgwood S, Czech L, Kim GA, Lakshminrusimha S, Schumacker PT, Steinhorn RH, Farrow KN. Cyclic stretch induces inducible nitric oxide synthase and soluble guanylate cyclase in pulmonary artery smooth muscle cells. Int J Mol Sci 14(2):4334-48, 2013.
333. Shyu KG, Chao YM, Wang BW, Kuan P. Regulation of discoidin domain receptor 2 by cyclic mechanical stretch in cultured rat vascular smooth muscle cells. Hypertension 46(3):614-621, 2005.
334. Shyu KG, Wang BW, Kuan P, Chang H. RNA interference for discoidin domain receptor 2 attenuates neointimal formation in balloon injured rat carotid artery. Arterioscler Thromb Vasc Biol 28(8):1447-1453, 2008.
335. Songu-Mize E, Jacobs M, Shreves A. Acute cyclic stretch induces upregulation of the Na-pump of aortic smooth muscle cells in culture by cytoplasmic translocation [abstract]. FASEB J 13:351.5, 1999.
336. Songu-Mize E, Jacobs M. Effect of cyclic in vitro stretch on aortic smooth muscle cell p42 and p44 mitogen acticated kinases [abstract]. FASEB J 12(Part I):A403, 2342, 1998.
337. Songu-Mize E, Liu X, Hymel LJ. Effect of mechanical strain on expression of Na+, K+-ATPase  subunits in rat aortic smooth muscle cells. Amer J Med Sci 316(3):196-199, 1998.
338. Songu-Mize E, Liu X, Stones JE, Hymel LJ. Regulation of Na+, K+-ATPase -subunit expression by mechanical strain in aortic smooth muscle cells. Hypertension 27:827-832, 1996.
339. Songu-Mize E, Liu X. Effect of cyclic mechanical strain on expression of Na+, K+-ATPase  subunits in rat aortic smooth muscle cells [abstract]. Cellular Deformation: Mechanics and Mechanisms of Physiological Response Meeting, Atlanta GA, October 1997.
340. Songu-Mize E, Sevieux N, Liu X, Jacobs M. Effect of short-term cyclic stretch on sodium pump activity in aortic smooth muscle cells. Amer J Physiol Heart Circ Physiol 281:H2072-H2078, 2001.
341. Standley PR, Camaratta A, Nolan BP, Purgason CT, Stanley MA. Cyclic stretch induces vascular smooth muscle cell alignment via NO signaling. Am J Physiol Heart Circ Physiol 283(5):H1907-H1914, 2002.
342. Standley PR, Obards TJ, Martina CL. Cyclic stretch regulates autocrine IGF-I in vascular smooth muscle cells: implications in vascular hyperplasia. Am J Physiol Endocrinol Metab 276:E697-E705, 1999.
343. Standley PR, Stanley MA, Senechal P. Activation of mitogenic and antimitogenic pathways in cyclically stretched arterial smooth muscle. Am J Physiol Endocrinol Metab 281(6):E1165-E1171, 2001.
344. Stanley AG, Knight AL, Williams B. Mechanical strain sensitizes human vascular smooth muscle cells to angiotensin II. American Journal of Hypertension 13(4 Suppl 1):S12, 2000.
345. Stanley AG, Patel H, Knight AL, Williams B. Mechanical strain-induced human vascular matrix synthesis: the role of angiotensin II. J Renin Angiotensin Aldosterone Syst 1(1):32-35, 2000.
346. Stones J, Liu X, Hymel L, Songu-Mize E. Upregulation of Na+, K+-ATPase -1 subunit in aortic smooth muscle cells stretched in culture [abstract]. Hypertension 26:578, P158, 1995.
347. Su BY, Shontz KM, Flavahan NA, Nowicki PT. The effect of phenotype on mechanical stretch-induced vascular smooth muscle cell apoptosis. J Vasc Res 43(3):229-237, 2006.
348. Sumpio BE, Banes AJ, Link WG, Johnson G Jr. Enhanced collagen production by smooth muscle cells during repetitive mechanical stretching. Arch Surg 123(10):1233-1236, 1988.
FLEXCELL® INTERNATIONAL CORPORATION
23
349. Sumpio BE, Banes AJ. Response of porcine aortic smooth muscle cells to cyclic tensional deformation in culture. J Surg Res 44(6):696-701, 1988.
350. Tamura K, Chen YE, Lopez-Ilasaca M, Daviet L, Tamura N, Ishigami T, Akishita M, Takasaki I, Tokita Y, Pratt RE, Horiuchi M, Dzau VJ, and Umemura S. Molecular mechanism of fibronectin gene activation by cyclic stretch in vascular smooth muscle cells. J Biol Chem 275(44):34619-34627, 2000.
351. Tan W, Scott D, Belchenko D, Qi HJ, Xiao L. Development and evaluation of microdevices for studying anisotropic biaxial cyclic stretch on cells. Biomed Microdevices 10(6):869-882, 2008.
352. Tock J, Van Putten V, Stenmark KR, Nemenoff RA. Induction of SM--actin expression by mechanical strain in adult vascular smooth muscle cells is mediated through activation of JNK and p38 MAP kinase. Biochem Biophys Res Commun 301(4):1116-1121, 2003.
353. van Wamel AJ, Ruwhof C, van der Valk-Kokshoom LE, Schrier PI, van der Laarse A. The role of angiotensin II, endothelin-1 and transforming growth factor- as autocrine/paracrine mediators of stretch-induced cardiomyocyte hypertrophy. Mol Cell Biochem 218(1-2):113-124, 2001.
354. van Wamel AJ, Ruwhof C, van der Valk-Kokshoorn LJ, Schrier PI, van der Laarse A. Stretch-induced paracrine hypertrophic stimuli increase TGF-1 expression in cardiomyocytes. Mol Cell Biochem 236(1-2):147-153, 2002.
355. von Offenberg Sweeney N, Cummins PM, Birney YA, Redmond EM, Cahill PA. Cyclic strain-induced endothelial MMP-2: role in vascular smooth muscle cell migration. Biochemical and Biophysical Research Communications 320:325–333, 2004.
356. Walker-Caprioglio HM, Hunter DD, McGuire PG, Little SA, McGuffee LJ. Composition in situ and in vitro of vascular smooth muscle laminin in the rat. Cell Tissue Res 281(1):187-196, 1995.
357. Wedgwood S, Lakshminrusimha S, Schumacker PT, Steinhorn RH. Hypoxia inducible factor signaling and experimental persistent pulmonary hypertension of the newborn. Front Pharmacol 6:47, 2015.
358. Wernig F, Mayr M, Xu Q. Mechanical stretch-induced apoptosis in smooth muscle cells is mediated by 1-integrin signaling pathways. Hypertension 41(4):903-911, 2003.
359. Wiersbitzky M, Mills I, Sumpio BE, Gewirtz H. Chronic cyclic strain reduces adenylate cyclase activity and stimulatory G protein subunit levels in coronary smooth muscle cells. Exp Cell Res 210(1):52-55, 1994.
360. Wilson E, Mai Q, Sudhir K, Weiss RH, Ives HE. Mechanical strain induces growth of vascular smooth muscle cells via autocrine action of PDGF. J Cell Biol 123(3):741-747, 1993.
361. Wilson E, Vives F, Collins T, Ives HE. Strain-responsive regions in the platelet-derived growth factor-A gene promoter. Hypertension 31(1 Pt 2):170-175, 1998.
362. Yang Z, Noll G, Luscher TF. Calcium antagonists differently inhibit proliferation of human coronary smooth muscle cells in response to pulsatile stretch and platelet- derived growth factor. Circulation 88:832-836, 1993.
363. Yao QP, Xie ZW, Wang KX, Zhang P, Han Y, Qi YX, Jiang ZL. Profiles of long noncoding RNAs in hypertensive rats: long noncoding RNA XR007793 regulates cyclic strain-induced proliferation and migration of vascular smooth muscle cells. J Hypertens 35(6):1195-1203, 2017.
364. Yao QP, Zhang P, Qi YX, Chen SG, Shen BR, Han Y, Yan ZQ, Jiang ZL. The role of SIRT6 in the differentiation of vascular smooth muscle cells in response to cyclic strain. Int J Biochem Cell Biol 49:98-104, 2014.
365. Zampetaki A, Zhang Z, Hu Y, Xu Q. Biomechanical stress induces IL-6 expression in smooth muscle cells via Ras/Rac1-p38 MAPK-NF-B signaling pathways. Am J Physiol Heart Circ Physiol 288(6):H2946-H2954, 2005.
OTHER CARDIOVASCULAR CELLS
366. Balguid A, Rubbens MP, Mol A, Bank RA, Bogers AJ, van Kats JP, de Mol BA, Baaijens FP, Bouten CV. The role of collagen cross-links in biomechanical behavior of human aortic heart valve leaflets - relevance for tissue engineering. Tissue Eng 13(7):1501-1511, 2007.
367. Ballotta V, Driessen-Mol A, Bouten CV, Baaijens FP. Strain-dependent modulation of macrophage polarization within scaffolds. Biomaterials 35(18):4919-28, 2014.
368. Boerboom RA, Rubbens MP, Driessen NJ, Bouten CV, Baaijens FP. Effect of strain magnitude on the tissue properties of engineered cardiovascular constructs. Annals of Biomedical Engineering 36(2):244–253, 2008.

369. Clause KC, Tinney JP, Liu JL, Keller BB, Huard J, Tobita K. p38MAP-kinase regulates cardiomyocyte proliferation and contractile properties of engineered early embryonic cardiac tissue [abstract]. Weinstein Cardiovascular Development Research Conference, Indianapolis, IN, 2007.
370. Clause KC, Tinney JP, Liu LJ, Keller BB, Tobita K. Engineered early embryonic cardiac tissue increases cardiomyocyte proliferation by cyclic mechanical stretch via p38-MAP kinase phosphorylation. Tissue Engineering Part A 15(6):1373-1380, 2009.
371. Fisher CI, Chen J, Merryman WD. Calcific nodule morphogenesis by heart valve interstitial cells is strain dependent. Biomech Model Mechanobiol 12(1):5-17, 2013.
372. Foolen J, Baaijens F. Stress-fiber remodeling in 3D: ‘contact guidance vs stretch avoidance.’ J Biomech 45(Suppl 1):S422, 2012.
373. French KM, Maxwell JT, Bhutani S, Ghosh-Choudhary S, Fierro MJ, Johnson TD, Christman KL, Taylor WR, Davis ME. Fibronectin and cyclic strain improve cardiac progenitor cell regenerative potential in vitro. Stem Cells Int 2016:8364382, 2016.
374. Gupta V, Grande-Allen KJ. Effects of static and cyclic loading in regulating extracellular matrix synthesis by cardiovascular cells. Cardiovasc Res 72(3):375-383, 2006.
375. Hutcheson JD, Chen J, Sewell-Loftin MK, Ryzhova LM, Fisher CI, Su YR, Merryman WD. Cadherin-11 regulates cell-cell tension necessary for calcific nodule formation by valvular myofibroblasts. Arterioscler Thromb Vasc Biol 33(1):114-20, 2013.
376. Hutcheson JD, Venkataraman R, Baudenbacher FJ, Merryman WD. Intracellular Ca(2+) accumulation is strain-dependent and correlates with apoptosis in aortic valve fibroblasts. J Biomech 45(5):888-94, 2012.
377. Kapur NK, Deming CB, Kapur S, Bian C, Champion HC, Donahue JK, Kass DA, Rade JJ. Hemodynamic modulation of endocardial thromboresistance. Circulation 115(1):67-75, 2007.
378. Carrion K, Dyo J, Patel V, Sasik R, Mohamed SA, Hardiman G, Nigam V. The long non-coding HOTAIR is modulated by cyclic stretch and WNT/β-CATENIN in human aortic valve cells and is a novel repressor of calcification genes. PLoS One 9(5):e96577, 2014.
379. Klein G, Schaefer A, Hilfiker-Kleiner D, Oppermann D, Shukla P, Quint A, Podewski E, Hilfiker A, Schroder F, Leitges M, Drexler H. Increased collagen deposition and diastolic dysfunction but preserved myocardial hypertrophy after pressure overload in mice lacking PKC. Circ Res 96(7):748-755, 2005.
380. Krishnamurthy VK, Stout AJ, Sapp MC, Matuska B, Lauer ME, Grande-Allen KJ. Dysregulation of hyaluronan homeostasis during aortic valve disease. Matrix Biol 62:40-57, 2017.
381. Ku CH, Johnson PH, Batten P, Sarathchandra P, Chambers RC, Taylor PM, Yacoub MH, Chester AH. Collagen synthesis by mesenchymal stem cells and aortic valve interstitial cells in response to mechanical stretch. Cardiovasc Res 71(3):548-556, 2006.
382. Patel V, Carrion K, Hollands A, Hinton A, Gallegos T, Dyo J, Sasik R, Leire E, Hardiman G, Mohamed SA, Nigam S, King CC, Nizet V, Nigam V. The stretch responsive microRNA miR-148a-3p is a novel repressor of IKBKB, NF-B signaling, and inflammatory gene expression in human aortic valve cells. FASEB J 29(5):1859-68, 2015.
383. Rakesh K, Yoo B, Kim IM, Salazar N, Kim KS, Rockman HA. -Arrestin-biased agonism of the angiotensin receptor induced by mechanical stress. Sci Signal 3(125):ra46, 2010.
384. Tamiello C, Bouten CV, Baaijens FP. Competition between cap and basal actin fiber orientation in cells subjected to contact guidance and cyclic strain. Sci Rep 5:8752, 2015.
385. Throm Quinlan AM, Sierad LN, Capulli AK, Firstenberg LE, Billiar KL. Combining dynamic stretch and tunable stiffness to probe cell mechanobiology in vitro. PLoS ONE 6(8):e23272, 2011.
386. Tobita K, Garrison JB, Keller BB. Differential effects of cyclic stretch on embryonic ventricular cardiomyocyte and non-cardiomyocyte orientation. In: Cardiovascular Development and Congenital Malformations: Molecular & Genetic Mechanisms, Edited by Artman M, Benson DW, Srivastava D, Nakazawa M. Blackwell Futura Publishing:177-179, 2005.
387. Tobita K, Liu LJ, Janczewski AM, Tinney JP, Nonemaker JM, Augustine S, Stolz DB, Shroff SG, Keller BB. Engineered early embryonic cardiac tissue retains proliferative and contractile properties of developing embryonic myocardium. Am J Physiol Heart Circ Physiol 291(4):H1829-37, 2006.
388. van Geemen D, Driessen-Mol A, Baaijens FP, Bouten CV. Understanding strain-induced collagen matrix development in engineered cardiovascular tissues from gene expression profiles. Cell Tissue Res 352(3):727-37, 2013.
389. Ye F, Yuan F, Li X, Cooper N, Tinney JP, Keller BB. Gene expression profiles in engineered cardiac tissues respond to mechanical loading and inhibition of tyrosine kinases. Physiol Rep 1(5):e00078, 2013.