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, alpha nu beta 3- and alpha nu beta 5-integrins. Integrin expression and 7E3 binding in human umbilical venous endothelial cells, human umbilical venous smooth muscle cells, and human iliac arterial smooth muscle cells were observed in the following intensity: alpha nu beta 3 - human umbilical venous endothelial cells > human umbilical venous smooth muscle cells > human iliac arterial smooth muscle cells/alpha nu beta 5 - human iliac arterial smooth muscle cells > human umbilical venous smooth muscle cells > human umbilical venous endothelial cells. 7E3 binding correlated with alpha nu beta 3-expression in all cell types. Integrin-mediated cell functions were analysed with adhesion and spreading assays on vitronectin. In human umbilical venous endothelial cells, these functions were mediated by alpha nu beta 3 and in human iliac arterial smooth muscle cells by alpha nu beta 5. In human umbilical venous smooth muscle cells, both vitronectin receptors were involved. Abciximab potently inhibited alpha nu beta 3-mediated cell adhesion and spreading. With tirofiban, no significant inhibition of vascular cell functions was observed. The present data demonstrate that vitronectin-cell interactions in vascular cells are mediated via two distinct integrin-receptors, alpha 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 endothelium and in beta 3-integrin expressing vascular smooth muscle cells. (C) 2000 Elsevier Science B.V. All rights reserved.