P-selectin in arterial thrombosis.
P-selectin is a transmembrane protein present in the alpha granules of platelets and the Weibel-Palade bodies of endothelial cells. Following activation, it is rapidly translocated to the cell surface. P-selectin expression in platelets has been shown to be elevated in disorders associated with arterial thrombosis such as coronary artery disease, acute myocardial infarction, stroke, and peripheral artery disease. P-selectin mediates rolling of platelets and leukocytes on activated endothelial cells as well as interactions of platelets with leukocytes. Platelet P-selectin interacts with P-selectin glycoprotein ligand-1 (PSGL-1) on leukocytes to form platelet-leukocyte aggregates. Furthermore, this interaction of P-selectin with PSGL-1 induces the upregulation of tissue factor, several cytokines in leukocytes and the production of procoagulant microparticles, thereby contributing to a prothrombotic state. P-selectin is also involved in platelet-platelet interactions, i. e. platelet aggregation which is a major factor in arterial thrombosis. P-selectin interacts with platelet sulfatides, thereby stabilizing initial platelet aggregates formed by GPIIb/IIIa-fibrinogen bridges. Inhibtion of the P-selectin-sulfatide interaction leads to a reversal of platelet aggregation. Thus, P-selectin plays a significant role in platelet aggregation and platelet- leukocyte interactions, both important mechanisms in the development of arterial thrombosis.
Merten
M
M
Herzzentrum, Medizinische Klinik III, Kardiologie und Angiologie, Universitätsklinik Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany. michael_merten@yahoo.com
Thiagarajan
P
P
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000276:immunology* / Q000378:metabolism*; D001161:Arteriosclerosis / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers; D003328:Coronary Thrombosis / Q000276:immunology / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D019007:P-Selectin / Q000276:immunology* / Q000378:metabolism*; D015539:Platelet Activation / Q000276:immunology*; D013927:Thrombosis / Q000276:immunology* / Q000378:metabolism*
D015415:Biomarkers; D019007:P-Selectin