Semin Thromb Hemost 1998; 24(2): 151-156
DOI: 10.1055/s-2007-995834
Copyright © 1998 by Thieme Medical Publishers, Inc.

Transcellular Signaling and Pharmacological Modulation of Thrombin-Induced Production of Plasminogen Activator Inhibitor-1 in Vascular Smooth Muscle Cells

Garry X. Shen* , Song Ren* , John W. Fenton  II 
  • From the *Departments of Internal Medicine and Physiology, The University of Manitoba, Winnipeg, Manitoba, Canada, and the
  • †New York State Department of Health, Wadsworth Center for Laboratory and Research, Albany, New York.
Further Information

Publication History

Publication Date:
06 February 2008 (online)

Abstract

Thrombin formation is increased at the sites of vascular injury. Previous studies by our group and other groups indicated that the generation of plasminogen activator inhibitor-1 (PAI-1), the major physiological inhibitor for plasminogen activators, from cultured vascular smooth muscle cells (SMC) is elicited by thrombin. The present study demonstrates that the thrombin receptor, pertussis toxin-sensitive G protein, genistein-sensitive tyrosine kinase, phospholipase C, and protein kinase C may be involved in thrombin-induced PAI-1 production in cultured baboon aortic SMC. Forskolin and 8-bromo-cyclic AMP inhibited thrombin-induced PAI-1 production in cultured SMC. Treatment with hirulog-1, a synthetic thrombin receptor inhibitor, suppressed thrombin-induced PAI-1 generation at mRNA and protein levels in SMC. The results of the present study suggest that transmembrane receptor and multiple signal transduction systems are involved in thrombin-induced increase in PAI-1 transcription in vascular SMC. The production of PAI-1 stimulated by thrombin in vascular SMC may be pharmacologically modulated by thrombin receptor inhibitor.

    >