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Natriuretic factors and nitric oxide suppress plasminogen activator inhibitor-1 expression in vascular smooth muscle cells. Role of cGMP in the regulation of the plasminogen system.

Authors: Bouchie, JL  Hansen, H  Feener, EP 
Citation: Bouchie JL, etal., Arterioscler Thromb Vasc Biol. 1998 Nov;18(11):1771-9.
Pubmed: (View Article at PubMed) PMID:9812917

Increased expression of plasminogen activator inhibitor-1 (PAI-1) has been reported in atherosclerotic and balloon-injured vessels. Little is known regarding the factors and mechanisms that may negatively regulate PAI-1 expression. In this report, the effect of cGMP-coupled vasoactive hormones, including natriuretic factors and nitric oxide, on the regulation of PAI-1 expression in vascular smooth muscle cells was examined. Atrial natriuretic factor 1-28 (ANF) and C-type natriuretic factor-22 (CNP) reduced angiotensin II (Ang II)- and platelet-derived growth factor-stimulated PAI-1 mRNA expression in rat aortic smooth muscle cells by 50% to 70%, with corresponding reductions in PAI-1 protein release. Treatment of human aortic smooth muscle cells with CNP similarly inhibited both platelet-derived growth factor-induced PAI-1 mRNA expression and PAI-1 protein release by 50%. Dose-response studies revealed that the inhibitory effects of CNP and ANF on PAI-1 expression were concentration dependent, with IC50s of approximately 1 nmol/L for both natriuretic peptides. Ang II-stimulated PAI-1 expression was also inhibited by the nitric oxide donor S-nitroso-N-acetylpenicillamine. The membrane-permeant cGMP analogue 8-Br-cGMP reduced Ang II-stimulated PAI-1 expression by 60%, and an inhibitor of soluble guanylyl cyclase (1H-[1,2,4]oxadiazolo[4, 3-a]quinoxalin-1-one) significantly impaired the inhibitory effects of S-nitroso-N-acetylpenicillamine on Ang II-stimulated PAI-1 expression. Studies of PAI-1 mRNA stability in cells treated with actinomycin D showed that ANF did not alter PAI-1 mRNA half-life, suggesting that natriuretic factors reduce PAI-1 transcription. These data show that natriuretic factors and nitric oxide, via a cGMP-dependent mechanism, inhibit PAI-1 synthesis in vascular smooth muscle cells. Thus, cGMP-coupled vasoactive hormones may play an important role in suppressing vascular PAI-1 expression.


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CRRD Object Information
CRRD ID: 8547931
Created: 2014-02-28
Species: All species
Last Modified: 2014-02-28
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.