Platelet and Endothelial Cell Responses to Coronary Blood Flow
Wei Yin, Ph.D., Oklahoma State University
The goal of the present study was to investigate the effect of physiological and pathological shear stress on platelet and endothelial cell activities. A physiologically realistic 3D computational fluid dynamics (CFD) model of the left coronary artery under normal and stenosis conditions was developed to estimate blood flow induced shear stress. The 3D geometry 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-ω turbulence model. 3 typical shear stresses at normal, 80% stenosis and recirculation zone levels were applied to platelets and vascular endothelial cells in a programmable cone and plate shearing device. Platelet activation (CD62P expression), thrombogenicity and immune responses were measured using flow cytometry, a modified prothrombinase assay and ELISA respectively. 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 platelet activation and thrombogenicity are proportional to both shear stress amplitude and shear exposure time. Low-amplitude pulsatile shear stress present in the recirculation zones can significantly activate endothelial cells by enhancing ICAM-1 expression; as well as induce endothelial cell damage by enhancing tissue factor expression. However, elevated shear stress down regulated endothelial surface tissue factor expression. This study demonstrated that recirculation zone shear conditions may favor thrombosis, and lead to atherosclerotic lesion growth downstream of the stenosis.
Dr. Wei Yin is an assistant professor in the Department of Mechanical and Aerospace Engineering at Oklahoma State University. She received her Ph.D. in Biomedical Engineering at the State University of New York at Stony Brook in 2004, and was a post-doctoral research fellow in the Department of Pathology at the Weill Medical College of Cornell University in 2005-2007. Her research interests include flow induced vascular endothelial cell activation, platelet activation and thrombosis, endothelial cell - platelet interactions in atherosclerosis, Inflammatory responses in atherosclerosis, myocardial infarction and other cardiovascular diseases, numerical simulation of blood flow field under various disease conditions, and multi-scale modeling of vascular endothelial cells, platelets, leukocytes and erythrocytes interaction. Her current research has been funded by the American Heart Association and the National Science Foundation.