Factor Xa induces mitogenesis of coronary artery smooth muscle cell via activation of PAR-2.
Factor Xa-induced stimulation of coronary artery smooth muscle cells (CASMC) was investigated by analyzing [(3)H]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 [(3)H]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.
Department of Biochemistry, College of Science, and Bioproducts Research Center, Yonsei University, 120-749, Seoul, South Korea.
Bon Hun
BH
Koo
Kwang Hoe
KH
Chung
Ki Chul
KC
Hwang
Doo Sik
DS
Kim
D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D003331:Coronary Vessels / Q000166:cytology; D004789:Enzyme Activation; D015951:Factor Xa / Q000494:pharmacology*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008934:Mitogens / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000378:metabolism*
D008934:Mitogens; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D015951:Factor Xa