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

Qing Wang*, Andrea A. Domenighetti, Stephan C. Schäfer, Johanns Weber, Alexandra Simon, Marc P. Maillard, Thierry Pedrazzini, Ju Chen, Hans Anton Lehr, Michel Burnier

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)R1025-R1033
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume302
Issue number9
DOIs
StatePublished - May 1 2012

Keywords

  • Cardiac gene expression
  • Cardiac hypertrophy
  • Deoxycorticosterone-acetate

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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