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

• Published in: European journal of pharmacology 2000-02, Vol.390 (1), p.75-87
• Main Authors: Kintscher, Ulrich, Kappert, Kai, Schmidt, Gunther, Doerr, Gesine, Grill, Matthias, Wollert-Wulf, Brigitte, Graefe, Michael, Fleck, Eckart, Graf, Kristof
• Format: Article
• Language: English
• Subjects: Abciximab; Antibodies, Monoclonal - pharmacology; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Cell Adhesion - drug effects; Endothelial cell; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Fibrinolytic Agents - pharmacology; Flow Cytometry; Glycoprotein IIb/IIIa-inhibitor; Human; Humans; Iliac Artery - cytology; Iliac Artery - drug effects; Iliac Artery - metabolism; Immunoglobulin Fab Fragments - pharmacology; Immunohistochemistry; Integrin; Integrins - biosynthesis; Medical sciences; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Oligopeptides - isolation & purification; Oligopeptides - pharmacology; Pharmacology. Drug treatments; Receptors, Vitronectin - biosynthesis; Receptors, Vitronectin - drug effects; Receptors, Vitronectin - genetics; Reverse Transcriptase Polymerase Chain Reaction; Smooth muscle cell; Tirofiban; Tyrosine - analogs & derivatives; Tyrosine - pharmacology; Umbilical Veins - cytology; Umbilical Veins - drug effects; Umbilical Veins - metabolism; Vascular; Vitronectin; Vitronectin - metabolism
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(99)00912-7

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, αvβ3- and αvβ5-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: αvβ3 — human umbilical venous endothelial cells>human umbilical venous smooth muscle cells>human iliac arterial smooth muscle cells/αvβ5 — human iliac arterial smooth muscle cells>human umbilical venous smooth muscle cells>human umbilical venous endothelial cells. 7E3 binding correlated with αvβ3-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 αvβ3 and in human iliac arterial smooth muscle cells by αvβ5. In human umbilical venous smooth muscle cells, both vitronectin receptors were involved. Abciximab potently inhibited αvβ3-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, αvβ3 and αvβ5. Abciximab, which solely inhibits αvβ3-mediated cell functions, may be particularly effective in human endothelium and in β3-integrin expressing vascular smooth muscle cells.