P174	Cyclic stretch and shear stress: a complex interaction governing endothelial cell morphology and gene expression.
1P.Silacci, 1J.Fellay, 2M.Bueno, 2J.Weber, 2B.Sick, 1C.Chambaz, 1N.Stergiopulos
1EPFL/ Life Sciences/ Laboratory of Hemdoynamics and Cardiovascular Technology, Lausanne, CH; 2UNIL/ Integrative Genomic Center, Lausanne, CH.

Hemodynamic forces play an active role in vascular pathologies, particularly in relation to the localization of atherosclerotic lesions. It has been established that a disturbed shear stress characterized by a cyclic reversal flow affects the endothelial cell and leads to a changes in arterial function and nitric oxide production. In addition to shear stress, cyclic stretch is also thought to be a strong mechanical stimuli regulating endothelial cell function. In the past we developed a specific flow device able to combine pressure, cyclic stretch and shear stress, generating complete hemodynamic environments. In this study we used such perfusion device to investigate the real contribution of cyclic stretch on endothelial cell morphology and gene expression in a complete hemodynamic environments. Results presented here, demonstrate that cyclic stretch can induce changes in endothelial cell morphology only when applied in combination with low unidirectional shear stress and in particular with oscillatory shear stress. Moreover, using a microarray approach, we showed that the expression of only 22 out of 16'280 genes (0.2%) appeared to be down-regulated and one up-regulated by cyclic stretch in combination with an oscillatory shear stress as compared to cells exposed to oscillatory shear stress alone. No common regulators or common targets for the genes affected by cyclic stretch was found. Nevertheless, several genes appeared to be related to mitosis or cell proliferation. To assess whether cyclic stretch could effectively influence endothelial cell proliferation, we performed a series of experiments in which cells were seeded on the tubes at a sub confluent state. Cells were then exposed to oscillatory shear stress in presence or absence of a 4% cyclic stretch. In conclusion, cyclic stretch was shown to be a strong stimuli for endothelial cell morphology changes only in association with specific hemodynamic context, mimicking plaque-prone hemodynamics. We also provided evidences that cyclic stretch only weakly affect endothelial gene expression. Nevertheless this effect was enough to promote cell proliferation, suggesting that in vivo, preservation of vascular wall compliance, may promote proliferation-dependent repair process following local endothelial denudation at plaque-prone areas.

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