Molecular Signature of Mineralocorticoid Receptor Signaling in Cardiomyocytes: From Cultured Cells to Mouse Heart

• Type: Article in International Scientific Journal
• Date: 2010

Authors

Latouche, C (Author) Other; Sainte Marie, Y (Author) Other; Steenman, M (Author) Other; Castro-Chaves P (Author) FMUP; Naray Fejes Toth, A (Author) Other; Fejes Toth, G (Author) Other; Farman, N (Author) Other; Jaisser, F (Author) Other

Journal

Title: Endocrinology

Vol. 151

Pages: 4467-4476

ISSN: 0013-7227

Publisher: Endocrine Society

Indexing

ISI Web of Knowledge - 49 Citations

Scopus - 48 Citations

Other information

Authenticus ID: P-008-Q2H

DOI: 10.1210/en.2010-0237

Abstract (EN): Excess mineralocorticoid signaling is deleterious for cardiovascular functions, as demonstrated by the beneficial effects of mineralocorticoid receptor (MR) antagonism on morbidity and mortality in patients with heart failure. However, the understanding of signaling pathways after MR activation in the heart remains limited. We performed transcriptomic analyses in the heart of double-transgenic mice with conditional, cardiomyocyte-specific, overexpression of the MR (MRcardio mice) or the glucocorticoid receptor (GR; GRcardio mice). Some of the genes induced in MRcardio mice were selected for comparative evaluation (real time PCR) in vivo in the heart of mice and ex vivo in the MR-expressing cardiomyocyte H9C2 cell line after aldosterone or corticosterone treatment. We demonstrate that chronic MR overexpression in the heart results in a limited number of induced (n = 24) and repressed (n = 22) genes compared with their control littermates. These genes are specifically modulated by MR because there is limited overlap (three induced, four repressed) with the genes that are regulated in the heart of GRcardio mice (compared with control mice: 70 induced, 73 repressed). Interestingly, some MR-induced genes that are up-regulated in vivo in mice are also induced by 24-h aldosterone treatment in H9C2 cells, such as plasminogen activator inhibitor 1 and Serpina-3 (alpha 1-antichymotrypsin). The signaling pathways that are affected by long-term activation of MR may be of particular interest to design novel therapeutic targets in cardiac diseases. (Endocrinology 151: 4467-4476, 2010)

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10