Eptifibatide and 7E3, but not tirofiban, inhibit alpha(v)beta(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 alpha (v)beta (3) integrins on hum an aortic smooth muscle cells (HASMCs) or human umbilical vein endothelial cells (HUVECs). Abciximab binds alpha (III),beta (3) on platelets and alpha (v)beta (3) on HUVECs with similar affinity, whereas eptifibatide and tiro fiban are thought to be highly Specific for alpha (IIb)beta (3). The conclu sion that eptifibatide does not bind vascular alpha (v)beta (3) integrins m ay be premature, however, because recent studies have demonstrated that the affinity of alpha (v)beta (3) for various ligands, including antagonists, is subject to modulation. Methods and Results-Abciximab and 7E3, the anti-beta (3) integrin monoclona l antibody from which abciximab was derived, bound alpha (v)beta (3) on HAS MCs in a specific and saturable manner and with an affinity similar to bind ing to alpha (IIb)beta (3) on platelets. 7E3 and eptifibatide inhibited alp ha (v)beta (3)-mediated attachment of HASMCs to thrombospondin (TSP) and pr othrombin but had no effect on alpha (v)beta (5)- or beta (1)-mediated HASM C attachment to vitronectin-, collagen-, or fibronectin-coated or noncoated tissue culture plates. The inhibitory effect of eptifibatide was similar i n magnitude and not additive to that of 7E3. Eptifibatide and 7E3 inhibited alpha (v)beta (3)-mediated attachment of HUVECs. Tirofiban had only nonspe cific effects on HASMC attachment to extracellular matrix proteins. In cell proliferation assays, eptifibatide inhibited alpha (v)beta (3)-mediated re sponses to soluble TSP by HASMCs and beta (3) integrin-expressing HEK cells . Conclusions-Eptifibatide and 7E3, but not tirofiban, specifically inhibit a lpha (v)beta (3)-mediated binding of human smooth muscle and endothelial ce lls.