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(Circulation. 2001;104:582.)
© 2001 American Heart Association, Inc.

Basic Science Reports

Eptifibatide and 7E3, but Not Tirofiban, Inhibit _vß₃ Integrin–Mediated Binding of Smooth Muscle Cells to Thrombospondin and Prothrombin

Manjiri Lele, MD; Mansoor Sajid, MD, PhD; Nadeem Wajih, PhD; George A. Stouffer, MD

From the Program in Molecular Cardiology, University of North Carolina, Chapel Hill.

Correspondence to George A. Stouffer, MD, 324 Burnett-Womack Building, CB 7075, University of North Carolina, Chapel Hill, NC 27599-7075. E-mail rstouff{at}med.unc.edu

Background— Our objective was to determine whether abciximab, eptifibatide, or tirofiban inhibited ligand binding to _vß₃ integrins on human aortic smooth muscle cells (HASMCs) or human umbilical vein endothelial cells (HUVECs). Abciximab binds _IIbß₃ on platelets and _vß₃ on HUVECs with similar affinity, whereas eptifibatide and tirofiban are thought to be highly specific for _IIbß₃. The conclusion that eptifibatide does not bind vascular _vß₃ integrins may be premature, however, because recent studies have demonstrated that the affinity of _vß₃ for various ligands, including antagonists, is subject to modulation.

Methods and Results— Abciximab and 7E3, the anti–ß₃ integrin monoclonal antibody from which abciximab was derived, bound _vß₃ on HASMCs in a specific and saturable manner and with an affinity similar to binding to _IIbß₃ on platelets. 7E3 and eptifibatide inhibited _vß₃-mediated attachment of HASMCs to thrombospondin (TSP) and prothrombin but had no effect on _vß₅- or ß₁-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 _vß₃-mediated attachment of HUVECs. Tirofiban had only nonspecific effects on HASMC attachment to extracellular matrix proteins. In cell proliferation assays, eptifibatide inhibited _vß₃-mediated responses to soluble TSP by HASMCs and ß₃ integrin–expressing HEK cells.

Conclusions— Eptifibatide and 7E3, but not tirofiban, specifically inhibit _vß₃-mediated binding of human smooth muscle and endothelial cells.

Key Words: receptors • vitronectin • thrombin • angioplasty • muscle, smooth

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