title: Individual and combined effects of shear stress magnitude and spatial gradient on endothelial cell gene expression.
abstract: The apparent tendency of atherosclerotic lesions to form in complex blood flow environments has led to many theories regarding the importance of hemodynamic forces in endothelium-mediated atherosusceptibility. The effects of shear stress magnitude and spatial shear stress gradient on endothelial cell gene expression in vitro were examined in this study. Converging-width flow channels were designed to impose physiological ranges of shear stress gradient and magnitude on porcine aortic endothelial cells, and real-time quantitative PCR was performed to evaluate their expression of five genes of interest. Although vascular cell adhesion molecule-1 expression was insensitive to either variable, each of the remaining genes exhibited a unique dependence on shear stress magnitude and gradient. Endothelial nitric oxide synthase showed a strong positive dependence on magnitude but was insensitive to gradient. The expression of c-jun was weakly correlated with magnitude and gradient, without an interaction effect. Monocyte chemoattractant protein-1 expression varied inversely with gradient and also depended on the interaction of gradient with magnitude. Intercellular adhesion molecule-1 expression also exhibited an interaction effect, and increased with shear magnitude. These results support the notion that vascular endothelial cells are able to sense shear gradient and magnitude independently.
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: LaMack
authors.forename: Morton H
authors.initials: MH
authors.lastname: Friedman
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003198:Computer Simulation; D016207:Cytokines / Q000378:metabolism*; D042783:Endothelial Cells / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D007155:Immunologic Factors / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008955:Models, Cardiovascular; D033081:Shear Strength; D013314:Stress, Mechanical; D013552:Swine
chemical_list: D016207:Cytokines; D007155:Immunologic Factors