98. Vitronectin receptor (α_v, β₃) mediates platelet adhesion to the luminal aspect of activated endothelium. Implications for reperfusion in acute myocardial infarction (AMI)

Platelet interaction with endothelium plays an important role in the pathophysiology of thromboembolic and inflammatory events during reperfusion. We investigated the role of vitronectin receptor (integrin 03) for platelet adhesion to confluent monolayers of cultured human umbilical vein endothelial cells (HUVEC). HUVECs were incubated for 1, 4, and 24 h with plasma obtained from patients with AMI before and 8, 24, 48, 72, 96 h after successful direct PTCA of the infarcted coronary vessel. Platelet adhesion and surface expression of integrin α_vβ₃ on the luminal aspect of HUVECs was then determined by flow cytometry. Platelet-toendothelium adhesion was significantly enhanced after 24 h plasma incubation compared to l h incubation in reperfusion samples that was inhibitable (50%) by 500 nM RGDS peptide (p<0.001). Concomitantly, surface expression of Ov3 on the luminal aspect of endothelium also increased (p<0.01) as verified by antibody LM609 and echistatin binding. Stimulation of HUVECS with a-thrombin (2 U/ml) for 10 minutes and with interleukin Iβ (HIβ) or tumour necrosis factor (TNFα) (100 pg/ml for 12 h also significantly increased platelet-to-endothelium adhesion that was inhibitable by RGDS, and α_vβ₃ surface expression. We conclude that activation of endothelium with early (thrombin) and late (HIβ, TNFα) inflammatory reactants results in enhanced platelet adhesion mediated by vitronectin receptor expressed on the luminal aspect of HUVECs. Platelet-endothelium adhesion might contribute significantly to mechanisms of reperfusion injury and might reveal interesting therapeutic perspectives.