title: Direct and indirect effects of aldosterone on cyclooxygenase-2 and interleukin-6 expression in rat cardiac cells in culture and after myocardial infarction.
abstract: Aldosterone contributes to cardiac failure, which is associated with induction of inflammatory mediators. Moreover, aldosterone was shown to induce a vascular inflammatory phenotype in the rat heart. Using Western blotting and/or real-time RT-PCR, we examined the effect of aldosterone on the expression of the proinflammatory molecules, cyclooxygenase-2 (COX-2), and IL-6 in neonatal rat ventricular cardiac myocytes and fibroblasts as well as in adult cardiomyocytes after myocardial infarction. In cardiomyocytes, aldosterone induced COX-2 but not IL-6 expression. After 4-18 h of stimulation with 1 microm aldosterone, a significant increase in COX-2 protein expression was observed, preceded by an increase of COX-2 mRNA levels. After 18 h treatment, 100 nm and 1 microm aldosterone increased COX-2 protein amount by 2- and 4-fold, respectively. Consistently, aldosterone increased by 2.5-fold prostaglandin E(2) secretion in cardiomyocytes. In cardiac fibroblasts, aldosterone increased neither COX-2 nor IL-6 mRNA expression. Interestingly, prostaglandin E(2) (100 nm) strongly induced both proinflammatory molecules in fibroblasts and cardiomyocytes. Our results indicate that aldosterone directly induces COX-2 expression in cardiomyocytes and suggest that the subsequent increase in prostaglandin secretion may act in an autocrine and/or paracrine manner inducing in turn COX-2 and IL-6 expression. In vivo, myocardial infarction strongly increased both COX-2 and IL-6 expression in ventricular cardiomyocytes. Administration of the aldosterone antagonist RU28318 completely prevented COX-2 induction by infarction and partially inhibited the increase in IL-6 mRNA. These data suggest that after myocardial infarction, mineralocorticoid receptor activity is responsible for COX-2 induction and indirectly participates in IL-6 expression in cardiomyocytes.
authors.affiliation: Division of Endocrinology and Diabetology, University Hospital, 24 rue Micheli-du-Crest, CH-1211 Geneva 14, Switzerland. rebsamenmichela@hotmail.com.
authors.forename: Michela C
authors.initials: MC
authors.lastname: Rebsamen
authors.forename: Emeline
authors.initials: E
authors.lastname: Perrier
authors.forename: Christine
authors.initials: C
authors.lastname: Gerber-Wicht
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Benitah
authors.forename: Ursula
authors.initials: U
authors.lastname: Lang
mesh_terms: D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006352:Heart Ventricles / Q000166:cytology; D015850:Interleukin-6 / Q000235:genetics*; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D009203:Myocardial Infarction / Q000276:immunology / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D007527:Isoenzymes; D000450:Aldosterone; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone