This Article Full Text Full Text (PDF) All Versions of this Article: 145/7/3135    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rebsamen, M. C. Articles by Lang, U. Search for Related Content PubMed PubMed Citation Articles by Rebsamen, M. C. Articles by Lang, U.

Direct and Indirect Effects of Aldosterone on Cyclooxygenase-2 and Interleukin-6 Expression in Rat Cardiac Cells in Culture and after Myocardial Infarction

Division of Endocrinology and Diabetology (M.C.R., C.G.-W., U.L.), University Hospital, CH-1211 Geneva, Switzerland; and Institut National de la Santé et de la Recherche Médicale U390-EA 3759 (E.P., J.-P.B.), CHU Arnaud de Villeneuve, 34295 Montpellier, France

Address all correspondence and requests for reprints to: Michela Rebsamen, Ph.D., Division of Endocrinology and Diabetology, University Hospital, 24 rue Micheli-du-Crest, CH-1211 Geneva 14, Switzerland. E-mail: rebsamenmichela{at}hotmail.com.

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 µM 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 µM aldosterone increased COX-2 protein amount by 2- and 4-fold, respectively. Consistently, aldosterone increased by 2.5-fold prostaglandin E₂ secretion in cardiomyocytes. In cardiac fibroblasts, aldosterone increased neither COX-2 nor IL-6 mRNA expression. Interestingly, prostaglandin E₂ (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.

This article has been cited by other articles:

				J.-Y. Qian, P. Harding, Y. Liu, E. Shesely, X.-P. Yang, and M. C. LaPointe Reduced Cardiac Remodeling and Function in Cardiac-Specific EP4 Receptor Knockout Mice With Myocardial Infarction Hypertension, February 1, 2008; 51(2): 560 - 566. [Abstract] [Full Text] [PDF]

				Z. Guo, Z. Xia, J. Jiang, and J. H. McNeill Downregulation of NADPH oxidase, antioxidant enzymes, and inflammatory markers in the heart of streptozotocin-induced diabetic rats by N-acetyl-L-cysteine Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1728 - H1736. [Abstract] [Full Text] [PDF]

				M. A. Frias, M. C. Rebsamen, C. Gerber-Wicht, and U. Lang Prostaglandin E2 activates Stat3 in neonatal rat ventricular cardiomyocytes: A role in cardiac hypertrophy Cardiovasc Res, January 1, 2007; 73(1): 57 - 65. [Abstract] [Full Text] [PDF]