title: Sodium restriction modulates innate immunity and prevents cardiac remodeling in a rat model of metabolic syndrome.
abstract: In the view of the relationships between excessive sodium intake, immunity and target organ damage, we hypothesized that reduction in dietary sodium would be beneficial in the prevention of cardiac alterations through a restrained local immunity response in a rat model of metabolic syndrome. Sprague-Dawley rats were fed a 60% fructose diet with either a normal sodium (0.64% NaCl) or a low sodium content (<0.01% NaCl) for 8weeks. After 4weeks, rats were infused or not with angiotensin II (200ng·kg-1·min-1, sc) for 4weeks. Tail-cuff blood pressure was determined in conscious rats. Heart and left ventricle weight, cardiomyocyte size, and cardiac fibrosis were evaluated. We performed a transcriptomic analysis in order to identify differentially regulated cardiac mRNAs between normal and low sodium diets. We validated those results using qPCR and immunohistochemistry. Angiotensin II-induced blood pressure rise was blunted (~50%) in the low-sodium fed rats while cardiac hypertrophy and fibrosis were prevented. Transcriptomic analysis revealed 66 differentially regulated genes including 13 downregulated genes under the low sodium diet and implicated in the innate immune response. This was confirmed by reduced cardiac macrophages infiltration under the low sodium diet. Dietary sodium restriction prevents structural alterations of the heart of rats with fructose-induced insulin resistance and angiotensin II-hypertension. The reduction of cardiac inflammation and macrophage infiltration suggests that innate immunity has an important role in the beneficial effect of sodium restriction on cardiac remodeling.
authors.affiliation: INSERM U1046, CNRS UMR 91214, Montpellier University, Montpellier, France. Electronic address: bernard.jover@inserm.fr.
authors.forename: Bernard
authors.initials: B
authors.lastname: Jover
authors.affiliation: Institute of Functional Genomics, CNRS UMR5203, INSERM U1191, Montpellier University, Montpellier, France; Laboratory of Biostatistics, Informatics and Pharmaceutical Physics, Montpellier University, Montpellier, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Reynes
authors.affiliation: BioCommunication en CardioMétabolique (BC(2)M), Montpellier University, Montpellier, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Rugale
authors.affiliation: LaPEC EA4278, Avignon University, Avignon, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Reboul
authors.affiliation: BioCommunication en CardioMétabolique (BC(2)M), Montpellier University, Montpellier, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Jeanson
authors.affiliation: BioCommunication en CardioMétabolique (BC(2)M), Montpellier University, Montpellier, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Tournier
authors.affiliation: BioCommunication en CardioMétabolique (BC(2)M), Montpellier University, Montpellier, France.
authors.forename: Anne Dominique
authors.initials: AD
authors.lastname: Lajoix
authors.affiliation: BioCommunication en CardioMétabolique (BC(2)M), Montpellier University, Montpellier, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Desmetz
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000178:diet therapy / Q000276:immunology; D004039:Diet, Sodium-Restricted; D004040:Dietary Carbohydrates / Q000009:adverse effects* / Q000494:pharmacology; D004195:Disease Models, Animal; D005355:Fibrosis; D005632:Fructose / Q000009:adverse effects* / Q000494:pharmacology; D007113:Immunity, Innate; D024821:Metabolic Syndrome / Q000139:chemically induced / Q000178:diet therapy / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000009:adverse effects / Q000494:pharmacology
chemical_list: D004040:Dietary Carbohydrates; D017673:Sodium Chloride, Dietary; D005632:Fructose
keywords: Cardiac hypertrophy; Fibrosis; Inflammation; Innate immunity; Low sodium diet; Macrophage