期刊
THROMBOSIS RESEARCH
卷 150, 期 -, 页码 44-50出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.thromres.2016.12.003
关键词
Endothelial cells; Platelets; Shear stress; PECAM-1; ICAM-1
资金
- Div Of Engineering Education and Centers
- Directorate For Engineering [1359167] Funding Source: National Science Foundation
Introduction: Both vascular endothelial cells and platelets are sensitive to blood flow induced shear stress. We have recently reported that platelet-endothelial cell interaction could greatly affect platelet activation under flow. In the present study, we aimed to investigate how platelet-endothelial cell interaction affected endothelial cell inflammatory responses under flow. Materials and methods: Human coronary artery endothelial cells were exposed to normal or low pulsatile shear stress with or without the presence of platelets. Following shear exposure, endothelial cell ICAM-1 expression was measured using ELISA, Western blot and PCR; cell surface PECAM-1 expression/phosphorylation was measured using ELISA. Platelet adhesion to endothelial cells was quantified using immunofluorescence microscopy. To determine the role of PECAM-1 in platelet-endothelial cell interaction, endothelial cell PECAM-1 expression was suppressed using siRNA. Results: Pathological low shear stress induced a significant increase in endothelial cell ICAM-1 expression, at both protein and mRNA levels. Platelet adhesion to endothelial cells increased significantly under low shear stress, colocalizing with PECAM-1 at endothelial cell junctions. The presence of platelets inhibited low shear stressinduced ICAM-1 upregulation. When endothelial cell PECAM-1 expression was suppressed, platelet adhesion to endothelial cells under low shear stress decreased significantly; endothelial cell ICAM-1 expression was not affected by shear stress, with or without platelets. Conclusions: These results suggested that PECAM-1 could mediate platelet adhesion to endothelial cells under shear stress. Platelets binding to endothelial cells interfered with endothelial cell mechanotransduction through PECAM-1, affecting endothelial cell inflammatory responses towards pathological shear flow. (C) 2016 Elsevier Ltd. All rights reserved.
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