Vitronectin receptor (α(v)β₃) mediates platelet adhesion to the luminal aspect of endothelial cells: Implications for reperfusion in acute myocardial infarction

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)β₃) 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)β₃ 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)β₃ (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.