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1 Swiss Federal Institute of Technology, Laboratory of Hemodynamics and Cardiovascular Technology, Lausanne, Vaud, Switzerland
* To whom correspondence should be addressed. E-mail: veronica.gambillara{at}epfl.ch.
Hemodynamic forces play an active role in vascular pathologies, particularly in relation to the localization of atherosclerotic lesions. It has been established that low shear stress combined with cyclic reversal of flow direction (oscillatory shear stress) affects the endothelial cells and may lead to an initiation of plaque development. The aim of the study was to analyze the effect of hemodynamic conditions in arterial segments perfused in vitro, in the absence of other stimuli. Left common porcine carotid segments were mounted into an ex-vivo arterial support system and perfused 3 days under unidirectional high and low shear stress (6± 3 and 0.3± 0.1 dynes/cm2) or oscillatory shear stress (0.3± 3 dynes/cm2). Bradykinin (BK)-induced vasorelaxation was drastically decreased in arteries exposed to oscillatory shear stress as compared to unidirectional shear stress. Impaired nitric oxide (NO)-mediated vasodilation was correlated to changes in both eNOS gene expression and eNOS activation in response to BK. This study determined the flow-mediated effects on native tissue cells perfused with physiologically relevant flows and supports the hypothesis that oscillatory shear stress is a determinant factor in early stages of atherosclerosis. Indeed, oscillatory shear stress induces an endothelial dysfunction, whereas unidirectional shear stress preserves the function of endothelial cells. Endothelial dysfunction is directly mediated by a down-regulation of eNOS gene expression and activation; consequently, a decrease of NO production and/or bioavailability occurs.
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