title: Akt-mediated cardioprotective effects of aldosterone in type 2 diabetic mice.
abstract: Studies have shown that aldosterone would have angiogenic effects and therefore would be beneficial in the context of cardiovascular diseases. We thus investigated the potential involvement of aldosterone in triggering a cardiac angiogenic response in the context of type-2 diabetes and the molecular pathways involved. Male 3-wk-old aldosterone synthase (AS)-overexpressing mice and their control wild-type (WT) littermates were fed a standard or high-fat, high-sucrose (HFHS) diet. After 6 mo of diet treatment, mice were euthanized, and cardiac samples were assayed by RT-PCR, immunoblotting, and immunohistology. HFHS diet induced type-2 diabetes in WT (WT-D) and AS (AS-D) mice. VEGFa mRNAs decreased in WT-D (-43%, P<0.05 vs. WT) and increased in AS-D mice (+236%, P< 0.01 vs. WT-D). In WT-D mouse hearts, the proapoptotic p38MAPK was activated (P<0.05 vs. WT and AS-D), whereas Akt activity decreased (-64%, P<0.05 vs. WT). The AS mice, which exhibited a cardiac up-regulation of IGF1-R, showed an increase in Akt phosphorylation when diabetes was induced (P<0.05 vs. WT and AS-D). Contrary to WT-D mice, AS-D mouse hearts did not express inflammatory markers and exhibited a normal capillary density (P<0.05 vs. WT-D). To our knowledge, this is the first study providing new insights into the mechanisms whereby aldosterone prevents diabetes-induced cardiac disorders.
authors.affiliation: Unité Mixte de Recherche en Santé (UMR-S) 942, Institut National de la Santé et de la Recherche Médicale (INSERM), and Paris Diderot University, Paris, France; and.
authors.forename: Loubina
authors.initials: L
authors.lastname: Fazal
authors.affiliation: Unité Mixte de Recherche en Santé (UMR-S) 942, Institut National de la Santé et de la Recherche Médicale (INSERM), and.
authors.forename: Feriel
authors.initials: F
authors.lastname: Azibani
authors.affiliation: Unité Mixte de Recherche en Santé (UMR-S) 942, Institut National de la Santé et de la Recherche Médicale (INSERM), and Assistance Publique-Hôpitaux de Paris (AP-HP), Biochemistry Department, Lariboisiere Hospital, Paris, France;
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bihry
authors.affiliation: Unité Mixte de Recherche en Santé (UMR-S) 942, Institut National de la Santé et de la Recherche Médicale (INSERM), and Paris Diderot University, Paris, France; and.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Coutance
authors.affiliation: Unité Mixte de Recherche en Santé (UMR-S) 942, Institut National de la Santé et de la Recherche Médicale (INSERM), and.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Polidano
authors.affiliation: Unité Mixte de Recherche en Santé (UMR-S) 942, Institut National de la Santé et de la Recherche Médicale (INSERM), and.
authors.forename: Régine
authors.initials: R
authors.lastname: Merval
authors.affiliation: Unité Mixte de Recherche en Santé (UMR-S) 942, Institut National de la Santé et de la Recherche Médicale (INSERM), and.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vodovar
authors.affiliation: Unité Mixte de Recherche en Santé (UMR-S) 942, Institut National de la Santé et de la Recherche Médicale (INSERM), and Assistance Publique-Hôpitaux de Paris (AP-HP), Biochemistry Department, Lariboisiere Hospital, Paris, France; Paris Descartes University, Paris, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Launay
authors.affiliation: Unité Mixte de Recherche en Santé (UMR-S) 942, Institut National de la Santé et de la Recherche Médicale (INSERM), and Paris Diderot University, Paris, France; and.
authors.forename: Claude
authors.initials: C
authors.lastname: Delcayre
authors.affiliation: Unité Mixte de Recherche en Santé (UMR-S) 942, Institut National de la Santé et de la Recherche Médicale (INSERM), and Assistance Publique-Hôpitaux de Paris (AP-HP), Biochemistry Department, Lariboisiere Hospital, Paris, France; Paris Diderot University, Paris, France; and jane-lise.samuel@inserm.fr.
authors.forename: Jane-Lise
authors.initials: JL
authors.lastname: Samuel
mesh_terms: D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D019405:Cytochrome P-450 CYP11B2 / Q000096:biosynthesis / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D059305:Diet, High-Fat; D006321:Heart / Q000187:drug effects; D006929:Hyperaldosteronism / Q000503:physiopathology; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis
chemical_list: D001786:Blood Glucose; D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt
keywords: IGF-1 receptor; heart; insulin; physiopathology