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The goal of the present study was to develop a physiologically realistic 3D computational fluid dynamics (CFD) model of the left coronary artery under normal and disease conditions to estimate blood flow induced shear stress, and then use the computed shear stress to stimulate vascular endothelial cells in vitro. A 3D geometry of the left coronary artery was built in ProE and the CFD analysis of the flow field was carried out in Fluent (v 6.23) under normal, 30%, 60% and 80% stenosis conditions. The transient blood flow velocity and shear stress were solved using a k-omega turbulence model. 3 typical shear stresses at normal, 80% stenosis and recirculation zone levels were applied to vascular endothelial cells in a cone and plate shearing device. Endothelial cell activation and injury induced by shear stress were measured by cell surface ICAM-1 and tissue factor expression, using fluorescence microscopy. Results demonstrated that oscillatory low shear stress present in the recirculation zones can significantly activate endothelial cells by enhancing ICAM-1 expression; while elevated shear stress at stenosis can induce endothelial cell damage by enhancing tissue factor expression. This study demonstrated that the combination of CFD and in vitro studies provided an efficient way to investigate the mechanism of blood flow induced mechanical stress on cardiovascular disease development in vivo.