Effects of abciximab and tirofiban on vitronectin receptors in human endothelial and smooth muscle cells

Glycoprotein IIb/IIIa blockade by abciximab and tirofiban, non-peptidergic inhibitors, leads to sustained clinical benefits in the treatment of acute coronary syndromes. The purpose of this study was to clarify the functional effects of abciximab and tirofiban on vascular vitronectin receptors, alph a nu beta 3- and alpha nu beta 5-integrins. Integrin expression and 7E3 bin ding in human umbilical venous endothelial cells, human umbilical venous sm ooth muscle cells, and human iliac arterial smooth muscle cells were observ ed in the following intensity: alpha nu beta 3 - human umbilical venous end othelial cells > human umbilical venous smooth muscle cells > human iliac a rterial smooth muscle cells/alpha nu beta 5 - human iliac arterial smooth m uscle cells > human umbilical venous smooth muscle cells > human umbilical venous endothelial cells. 7E3 binding correlated with alpha nu beta 3-expre ssion in all cell types. Integrin-mediated cell functions were analysed wit h adhesion and spreading assays on vitronectin. In human umbilical venous e ndothelial cells, these functions were mediated by alpha nu beta 3 and in h uman iliac arterial smooth muscle cells by alpha nu beta 5. In human umbili cal venous smooth muscle cells, both vitronectin receptors were involved. A bciximab potently inhibited alpha nu beta 3-mediated cell adhesion and spre ading. With tirofiban, no significant inhibition of vascular cell functions was observed. The present data demonstrate that vitronectin-cell interacti ons in vascular cells are mediated via two distinct integrin-receptors, alp ha nu beta 3 and alpha nu beta 5. Abciximab, which solely inhibits alpha nu beta 3-mediated cell functions, may be particularly effective in human end othelium and in beta 3-integrin expressing vascular smooth muscle cells. (C ) 2000 Elsevier Science B.V. All rights reserved.