Akt‐mediated cardioprotective effects of aldosterone in type 2 diabetic mice. Issue 6 (20th February 2014)

• Record Type: Journal Article
• Authors: Fazal, Loubina; Azibani, Feriel; Bihry, Nicolas; Coutance, Guillaume; Polidano, Evelyne; Merval, Régine; Vodovar, Nicolas; Launay, Jean‐Marie; Delcayre, Claude; Samuel, Jane‐Lise
• Is Part Of: FASEB journal. Volume 28:Issue 6(2014)
• Page Start: 2430
• Page End: 2440
• Publication Date: 2014-02-20
• Subjects: physiopathology -- heart -- insulin -- IGF‐1 receptor; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.13-239822
• Languages: English
• ISSNs: 0892-6638

Abstract

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.—Fazal, L., Azibani, F., Bihry, N., Coutance, G., Polidano, E., Merval, R., Vodovar, N., Launay, J.‐M., Delcayre, C., Samuel, J.‐L. Akt‐mediated cardioprotective effects of aldosterone in type 2 diabetic mice. FASEB J . 28, 2430–2440 (2014). www.fasebj.org