BETA(3) INTEGRINS ARE UP-REGULATED AFTER VASCULAR INJURY AND MODULATETHROMBOSPONDIN-INDUCED AND THROMBIN-INDUCED PROLIFERATION OF CULTUREDSMOOTH-MUSCLE CELLS

Background-Treatment with an antibody that binds beta(3) integins (abc iximab; c7E3 Fab) at the time of coronary angioplasty decreases the ne ed far repeat revascularization. Two potential mechanisms have been pr oposed to explain this effect: (1) inhibition of platelet aggregation or (2) interruption of ligand binding to beta(3) integrins on the smoo th muscle cell (SMC) surface. We examined the latter hypothesis by det ermining (1) if beta(3) integrin expression is upregulated after vascu lar injury in the baboon, (2) if 7E3 binds beta(3) integrins on cultur ed SMC, and (3) if beta(3) integrin activation plays a role in prolife ration of cultured SMC. Methods and Results-Results demonstrated that immunostaining for beta(3) integrins was present in the neointima 1 we ek after balloon withdrawal injury of baboon brachial arteries and tha t beta(3) integrin expression colocalized with alpha-actin-positive ce lls. In contrast, staining for beta(3) integrins was undetectable in c ontralateral uninjured brachial arteries. 7E3 bound to cultured human aortic SMC with an affinity (K-D=3.3 nmol/L) similar to 7E3 binding to endothelial cells or platelets. Cotreatment with 7E3 partially inhibi ted thrombospondin-induced or alpha-thrombin-induced proliferation but not PDGF-induced or serum-induced proliferation. Conclusions-In summa ry, these studies demonstrate that vascular cell beta(3) integrin expr ession is increased after injury, that 7E3 binds to cultured SMC with high affinity, and that beta(3) activation is important for thrombospo ndin-induced or alpha-thrombin-induced proliferation. These results su pport the hypothesis that beta(2) integrins play a role in SMC growth responses after balloon injury.