title: Aldosterone-specific activation of cardiomyocyte mineralocorticoid receptor in vivo.
abstract: Inappropriate mineralocorticoid receptor (MR) activation is involved in cardiac diseases. Whether and how aldosterone is involved in the deleterious effects of cardiac mineralocorticoid activation is still unclear. Mice overexpressing MR in cardiomyocytes and their controls were treated for 7 days with aldosterone, and cardiac transcriptome was analyzed. Aldosterone regulated 265 genes in cardiomyocyte-targeted MR overexpression mice. Forty three of these genes were also differentially expressed between untreated cardiomyocyte-targeted MR overexpression and controls mice, thus representing putative aldosterone-regulated genes in cardiomyocytes. Among these genes, we focused on connective tissue growth factor (CTGF). In vivo, in cardiomyocyte-targeted MR overexpression mice, aldosterone (but not corticosterone) induced CTGF expression (mRNA and protein) in cardiomyocytes. Ex vivo, aldosterone induced the binding of mineralocorticoid receptor to CTGF promoter and increased the expression of its transcript. Aldosterone induction of CTGF synthesis in cardiomyocytes seems pathologically relevant as the increase in CTGF observed in a model of heart failure (transverse aortic constriction) in rats was prevented by eplerenone, a mineralocorticoid receptor blocker. This study demonstrates that aldosterone specifically regulates gene expression in cardiomyocytes despite large prevalence of glucocorticoids in plasma.
authors.affiliation: Inserm U872, Team 1, Pierre and Marie Curie University, Paris, France.
authors.forename: Smail
authors.initials: S
authors.lastname: Messaoudi
authors.forename: Basile
authors.initials: B
authors.lastname: Gravez
authors.forename: Antoine
authors.initials: A
authors.lastname: Tarjus
authors.forename: Véronique
authors.initials: V
authors.lastname: Pelloux
authors.forename: Antoine
authors.initials: A
authors.lastname: Ouvrard-Pascaud
authors.forename: Claude
authors.initials: C
authors.lastname: Delcayre
authors.forename: Janelise
authors.initials: J
authors.lastname: Samuel
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Launay
authors.forename: Catalina
authors.initials: C
authors.lastname: Sierra-Ramos
authors.forename: Diego
authors.initials: D
authors.lastname: Alvarez de la Rosa
authors.forename: Karine
authors.initials: K
authors.lastname: Clément
authors.forename: Nicolette
authors.initials: N
authors.lastname: Farman
authors.forename: Fréderic
authors.initials: F
authors.lastname: Jaisser
mesh_terms: D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism; D000077545:Eplerenone; D051379:Mice; D008822:Mice, Transgenic; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism*; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D055513:Connective Tissue Growth Factor; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone