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.
Keywords:
Thrombin - plasminogen activator inhibitor-1 - smooth muscle cells - transcellular
signaling - hirulog
