Vitronectin Receptor (α v β 3 ) Mediates Platelet Adhesion to the Luminal Aspect of Endothelial Cells

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Abstract
Background Platelet interaction with endothelium plays an important role in the pathophysiology of coronary microcirculation. We assessed the role of the vitronectin receptor (integrin α v β 3 ) in platelet/endothelium adhesion. Methods and Results We investigated the effect 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 pretreatment with α-thrombin (2 U/mL) and recombinant human interleukin-1β. Platelet/endothelium adhesion was significantly enhanced by ≈20% after pretreatment of endothelium with patient plasma for 4 hours ( P <.05) compared with endothelium treated with pooled control plasma. Plasma-induced platelet/endothelium adhesion was, in part, RGD peptide dependent. Pretreatment of endothelial cells with α-thrombin or recombinant human interleukin-1β enhanced platelet/endothelium adhesion and surface expression of α v β 3 on the luminal aspect of endothelium ( P <.05). The adhesion of platelets, isolated platelet microparticles, and Chinese hamster ovary cells bearing human recombinant α IIb β 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. Conclusions The expression of vitronectin receptor exposed on the luminal aspect of activated endothelium is enhanced and mediates platelet/endothelium adhesion. Vitronectin receptor–mediated platelet attachment to activated endothelium during reperfusion may contribute to reperfusion injury and could be a target for antiadhesive therapy.