Factor Xa induces mitogenesis of coronary artery smooth muscle cell via activation of PAR-2

Abstract

Factor Xa-induced stimulation of coronary artery smooth muscle cells (CASMC) was investigated by analyzing [3H]thymidine incorporation, cell proliferation, and ERK-1/2 activation. Exposure of the cells to factor Xa evoked a time-dependent activation of ERK-1/2 with increased [3H]thymidine incorporation and cell proliferation. The factor Xa-induced ERK-1/2 activation was not desensitized by preincubation of the cells with thrombin. However, ERK-1/2 activation was markedly attenuated by prior exposure of the cells to protease-activated receptor-2 (PAR-2) activating peptide, SLIGKV. The mitogenic effect of factor Xa was significantly reduced in the presence of anti-PAR-2 monoclonal antibody. Several lines of experimental evidence indicate that factor Xa-induced mitogenesis of CASMC is a cellular process mediated by PAR-2 activation.