Reversible Cardiac Fibrosis and Heart Failure Induced by Conditional Expression of an Antisense mRNA of the Mineralocorticoid Receptor in Cardiomyocytes
Cardiac failure is a common feature in the evolution of cardiac disease. Among the determinants of cardiac failure, the reninangiotensin-aldosterone system has a central role, and antagonism of the mineralocorticoid receptor (MR) has been proposed as a therapeutic strategy. In this study, we questio...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 99; no. 10; pp. 7160 - 7165 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences
14.05.2002
National Acad Sciences The National Academy of Sciences |
Series | From the Cover |
Subjects | |
Online Access | Get full text |
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Summary: | Cardiac failure is a common feature in the evolution of cardiac disease. Among the determinants of cardiac failure, the reninangiotensin-aldosterone system has a central role, and antagonism of the mineralocorticoid receptor (MR) has been proposed as a therapeutic strategy. In this study, we questioned the role of the MR, not of aldosterone, on heart function, using an inducible and cardiac-specific transgenic mouse model. We have generated a conditional knock-down model by expressing solely in the heart an antisense mRNA directed against the murine MR, a transcription factor with unknown targets in cardiomyocytes. Within 2-3 mo, mice developed severe heart failure and cardiac fibrosis in the absence of hypertension or chronic hyperaldosteronism. Moreover, cardiac failure and fibrosis were fully reversible when MR antisense mRNA expression was subsequently suppressed. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 To whom reprint requests should be addressed. E-mail: jaisser@bichat.inserm.fr. Edited by Maurice B. Burg, National Institutes of Health, Bethesda, MD, and approved March 7, 2002 |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.102673599 |