Effects of Physiologically Relevant Shear Stress and Platelet-endothelial Cell Interaction on Platelet Activation and Platelet Microparticle Generation

Abstract

The major scope of this study was to investigate the effects of physiologically relevant shear stresses and platelet-endothelial cell (EC) interactions on platelet activation, and platelet microparticle (PMP) generation. In vitro experiments were conducted to investigate the effects of constant (0.1, 0.3, 1, and 3 Pa) and dynamic shear stress (normal, recirculation, and stenosis shear stress) on platelet activities and PMP generation. Platelets were exposed to these stresses, in a hemodynamic cone and plate shearing device, in the presence or absence of confluent human coronary artery EC (untreated or treated with TNF-alpha. Platelet activation was measured based on platelet surface P-selectin expression. Platelet surface glycoprotein GPIb-alpha expression and platelet microparticle generation were also measured simultaneously using flow cytometry. Experimental results indicated that altered shear stress can enhance platelet activation, impair GPIb-alpha expression, and cause PMP generation. Furthermore, the presence of untreated EC augmented these platelet responses, which indicated that platelet-EC interaction could modulate platelet function and activity. These results support the hypothesis that altered shear stress induced by disturbed blood flow conditions can activate platelets, which can be enhanced due to platelet-EC interactions, leading to the pathogenesis of various cardiovascular diseases.