Impact of salt on cardiac differential gene expression and coronary lesion in normotensive mineralocorticoid-treated mice

Wang, Qing; Domenighetti, Andrea A; Schäfer, Stephan C; Weber, Johanns; Simon, Alexandra; Maillard, Marc P; Pedrazzini, Thierry; Chen, Ju; Lehr, Hans-Anton; Burnier, Michel (2012). Impact of salt on cardiac differential gene expression and coronary lesion in normotensive mineralocorticoid-treated mice. American journal of physiology - regulatory, integrative and comparative physiology, 302(9), R1025-33. Bethesda, Md.: American Physiological Society 10.1152/ajpregu.00387.2011

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We previously reported that excess of deoxycorticosterone-acetate (DOCA)/salt-induced cardiac hypertrophy in the absence of hypertension in one-renin gene mice. This model allows us to study molecular mechanisms of high-salt intake in the development of cardiovascular remodeling, independently of blood pressure in a high mineralocorticoid state. In this study, we compared the effect of 5-wk low- and high-salt intake on cardiovascular remodeling and cardiac differential gene expression in mice receiving the same amount of DOCA. Differential gene and protein expression was measured by high-density cDNA microarray assays, real-time PCR and Western blot analysis in DOCA-high salt (HS) vs. DOCA-low salt (LS) mice. DOCA-HS mice developed cardiac hypertrophy, coronary perivascular fibrosis, and left ventricular dysfunction. Differential gene and protein expression demonstrated that high-salt intake upregulated a subset of genes encoding for proteins involved in inflammation and extracellular matrix remodeling (e.g., Col3a1, Col1a2, Hmox1, and Lcn2). A major subset of downregulated genes encoded for transcription factors, including myeloid differentiation primary response (MyD) genes. Our data provide some evidence that vascular remodeling, fibrosis, and inflammation are important consequences of a high-salt intake in DOCA mice. Our study suggests that among the different pathogenic factors of cardiac and vascular remodeling, such as hypertension and mineralocorticoid excess and sodium intake, the latter is critical for the development of the profibrotic and proinflammatory phenotype observed in the heart of normotensive DOCA-treated mice.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Service Sector > Institute of Pathology
UniBE Contributor:	Schäfer, Stephan
ISSN:	0363-6119
Publisher:	American Physiological Society
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:32
Last Modified:	05 Dec 2022 14:10
Publisher DOI:	10.1152/ajpregu.00387.2011
PubMed ID:	22403797
URI:	https://boris.unibe.ch/id/eprint/12445 (FactScience: 218789)