Eptifibatide and 7E3, but Not Tirofiban, Inhibit α v β 3 Integrin–Mediated Binding of Smooth Muscle Cells to Thrombospondin and Prothrombin

Background Our objective was to determine whether abciximab, eptifibatide, or tirofiban inhibited ligand binding to αv β3 integrins on human aortic smooth muscle cells (HASMCs) or human umbilical vein endothelial cells (HUVECs). Abciximab binds αIIb β3 on platelets and αv β3 on HUVECs with similar affinity, whereas eptifibatide and tirofiban are thought to be highly specific for αIIb β3 . The conclusion that eptifibatide does not bind vascular αv β3 integrins may be premature, however, because recent studies have demonstrated that the affinity of αv β3 for various ligands, including antagonists, is subject to modulation.Methods and Results Abciximab and 7E3, the anti–β3 integrin monoclonal antibody from which abciximab was derived, bound αv β3 on HASMCs in a specific and saturable manner and with an affinity similar to binding to αIIb β3 on platelets. 7E3 and eptifibatide inhibited αv β3 -mediated attachment of HASMCs to thrombospondin (TSP) and prothrombin but had no effect on αv β5 - or β1 -mediated HASMC attachment to vitronectin-, collagen-, or fibronectin-coated or noncoated tissue culture plates. The inhibitory effect of eptifibatide was similar in magnitude and not additive to that of 7E3. Eptifibatide and 7E3 inhibited αv β3 -mediated attachment of HUVECs. Tirofiban had only nonspecific effects on HASMC attachment to extracellular matrix proteins. In cell proliferation assays, eptifibatide inhibited αv β3 -mediated responses to soluble TSP by HASMCs and β3 integrin–expressing HEK cells.Conclusions Eptifibatide and 7E3, but not tirofiban, specifically inhibit αv β3 -mediated binding of human smooth muscle and endothelial cells.