Platelets attenuate endothelial cell's dynamic shear stress induced activation

The interaction between endothelial cells (ECs) and circulating platelets plays a critical role in cardiovascular pathogenesis. Their responses to blood flow induced shear stress can be either anti‐ or pro‐ atherogenic. The goal of this study was to determine if platelets adhere to ECs under altered flow conditions, and how it affects EC activity. ECs were subject to physiological or pathological dynamic shear stress with the presence of platelets. Platelet adhesion to ECs was examined using immunofluorescence microscopy; EC surface PECAM‐1 expression and phosphorylation was measured using a solid phase ELISA approach. Nitric oxide (NO) release from shear stress treated ECs was measured using a commercial EIA kit. Platelet adhesion to EC junctions was observed under both flow conditions. The presence of platelets caused a noticeable increase in EC PECAM‐1 expression and a decrease in PECAM‐1 phosphorylation under both physiological and pathological shear stress. NO release increased significantly in ECs under flow, independent of the presence of platelets. Since PECAM‐1 is a major mechanotransducer highly expressed at EC junctions, platelet adhesion to ECs can potentially affect EC mechanotransduction under flow, and the presence of platelets can attenuate EC activation by inhibiting PECAM‐1 phosphorylation. NO data suggests platelets do not alter the physiological response of ECs to shear stress, supporting the hypothesis that platelet physical contact with ECs, i.e., adhesion at the cell junctions, could potentially inhibit EC activation induced by flow.