ANTIBODY TO THROMBIN RECEPTOR INHIBITS NEOINTIMAL SMOOTH-MUSCLE CELL ACCUMULATION WITHOUT CAUSING INHIBITION OF PLATELET-AGGREGATION OR ALTERING HEMOSTATIC PARAMETERS AFTER ANGIOPLASTY IN RAT

An antibody was raised in rabbits against SFFLRNPSEDTFEQF peptide, whi ch is an NH2-terminal peptide of the thrombin-cleaved rat thrombin rec eptor. In vitro, the antibody inhibited rat smooth muscle cell prolife ration but had no effect on rat platelet aggregation or clotting time. These data indicate that the antibody is a specific blocker of the th rombin receptor-signaling pathway in rat smooth muscle cells but does not work as a blocker in rat platelets, suggesting the existence of a second thrombin receptor in the platelets. Using an in vivo balloon ca theter-induced injury model in rats, we examined the effect of the ant i-rat thrombin receptor IgG on intimal smooth muscle cell accumulation 2 weeks after angioplasty. Analysis of the ratio of intimal to medial cross-sectional areas showed that injection of immune IgG resulted in 43.7% and 53.1% reduction (P<0.01) of neointimal smooth muscle cell a ccumulation compared with saline and nonimmune IgG treatment, respecti vely. Moreover, the injection of immune IgG caused a significant decre ase of thrombin receptor mRNA expression and also 40.5% and 43.0% decr eases (P<0.01) of the proliferating cell nuclear antigen (PCNA) index in the intima compared with the PCNA index after saline and nonimmune IgG treatment, respectively. The suppression of the PCNA index was als o observed in the immune IgG-treated group at an early stage after ang ioplasty. These results suggest that thrombin receptor activation is i nvolved in the proliferation and accumulation of neointimal smooth mus cle cells induced by balloon injury.