VITRONECTIN RECEPTOR (ALPHA(NU)BETA(3)) MEDIATES PLATELET-ADHESION TOTHE LUMINAL ASPECT OF ENDOTHELIAL-CELLS - IMPLICATIONS FOR REPERFUSION IN ACUTE MYOCARDIAL-INFARCTION

Background Platelet interaction with endothelium plays an important ro le in the pathophysiology of coronary microcirculation. We assessed th e role of the vitronectin receptor (integrin alpha(v) beta(3)) in plat elet/endothelium adhesion. Methods and Results We investigated the eff ect on platelet/endothelium adhesion of plasma obtained from patients with acute myocardial infarction during reperfusion (before and 8, 24, 48, and 72 hours and 5 to 7 days after direct angioplasty) and with p retreatment with alpha-thrombin (2 U/mL) and recombinant human interle ukin-beta. Platelet/endothelium adhesion was significantly enhanced by approximate to 20% after pretreatment of endothelium with patient pla sma for 4 hours (P<.05) compared with endothelium treated with pooled control plasma. Plasma-induced platelet/endothelium adhesion was, in p art, RGD peptide dependent. Pretreatment of endothelial cells with alp ha-thrombin or recombinant human interleukin-1 beta enhanced platelet/ endothelium adhesion and surface expression of alpha(v) beta(3) on the luminal aspect of endothelium (P<.05). The adhesion of platelets, iso lated platelet microparticles, and Chinese hamster ovary cells bearing human recombinant alpha(IIb)beta(3) (platelet glycoprotein IIb-IIIa) to activated endothelial cells was inhibited by antiadhesive peptides GRGDSP and c(RGDfV) and monoclonal antibodies 4F10, LM609, and 7E3. Co nclusions The expression of vitronectin receptor exposed on the lumina l aspect of activated endothelium is enhanced and mediates platelet/en dothelium adhesion. Vitronectin receptor-mediated platelet attachment to activated endothelium during reperfusion may contribute to reperfus ion injury and could be a target for antiadhesive therapy.