Aldosterone increases plasminogen activator inhibitor-1 synthesis in rat cardiomyocytes.
Plasminogen activator inhibitor-1 (PAI-1) is an anti-thrombolytic factor that also promotes tissue fibrosis. Under certain conditions, exposure to aldosterone can result in cardiac fibrosis by an unknown mechanism. In the current study, we tested the hypothesis that PAI-1 is a mediator of aldosterone's fibrotic effects. Aldosterone increased levels of PAI-1 mRNA and protein in the H9c2 rat cardiac cell line, responses that could be blocked by the mineralocorticoid receptor (MR) antagonist spironolactone. Confocal microscopy confirmed an effect of aldosterone to increase PAI-1 expression with reversal by spironolactone. Aldosterone also increased PAI-1 expression in neonatal rat cardiomyocytes, which was again blocked by spironolactone. In the neonatal cardiomyocytes (but not the H9c2 cells), anti-transforming growth factor-beta1 antibody inhibited the PAI-1 response to aldosterone. In summary, aldosterone directly increased PAI-1 expression in two different cardiac muscle cell types, an effect that was dependent on MR. In the neonatal cells, there appeared to be a requirement for transforming growth factor-beta1.
Chun
Tae-Yon
TY
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA. tchun@iupui.edu
Pratt
J Howard
JH
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects*; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D013148:Spironolactone / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
D000451:Mineralocorticoid Receptor Antagonists; D017395:Plasminogen Activator Inhibitor 1; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D013148:Spironolactone; D000450:Aldosterone