title: Reversible cardiac fibrosis and heart failure induced by conditional expression of an antisense mRNA of the mineralocorticoid receptor in cardiomyocytes.
abstract: Cardiac failure is a common feature in the evolution of cardiac disease. Among the determinants of cardiac failure, the renin-angiotensin-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.
authors: Institut National de la Santé et de la Recherche Médicale U478, Hôpital Bichat-Claude Bernard, AP-HP, Federative Institute of Research 02, 75870 Paris, France.
authors: Ahmed T
authors: AT
authors: Beggah
authors: Brigitte
authors: B
authors: Escoubet
authors: Stefania
authors: S
authors: Puttini
authors: Stephane
authors: S
authors: Cailmail
authors: Vanessa
authors: V
authors: Delage
authors: Antoine
authors: A
authors: Ouvrard-Pascaud
authors: Brigitte
authors: B
authors: Bocchi
authors: Michel
authors: M
authors: Peuchmaur
authors: Claude
authors: C
authors: Delcayre
authors: Nicolette
authors: N
authors: Farman
authors: Frederic
authors: F
authors: Jaisser
mesh_terms: D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary; D004195:Disease Models, Animal; D005355:Fibrosis; D015870:Gene Expression; D006321:Heart; D006333:Heart Failure / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D008969:Molecular Sequence Data; D009206:Myocardium / Q000166:cytology / Q000473:pathology*; D016372:RNA, Antisense; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism*; D013148:Spironolactone / Q000494:pharmacology; D020257:Ventricular Remodeling
chemical_list: D018076:DNA, Complementary; D000451:Mineralocorticoid Receptor Antagonists; D016372:RNA, Antisense; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone