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- Title
P610 Akt-mediated cardioprotective effects of aldosterone in type 2 diabetic mice.
- Authors
Fazal, L; Azibani, F; Coutance, G; Birhy, N; Polidano, E; Merval, R; Vodovar, N; Launay, JM; Delcayre, C; Samuel, JL
- Abstract
Purpose: 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.Procedure: 3 week-old male mice, overexpressing aldosterone-synthase (AS), and their controls littermates (WT) were fed with a standard or high fat, high sucrose (HFHS) diet. After 6 months of diet, mice were sacrificed and cardiac samples were assayed by RT-PCR, immuno-blotting and -histology.Findings: HFHS-diet induced type-2 diabetes (D) in WT and AS mice. VEGFa mRNAs were decreased in WT-D (-43%, P<0.05 vs. WT) while increased in AS-D mice (+236%, P<0.01 vs. WT-D). In WT-D hearts, the proapoptotic p38-MAPK was activated (P<0.05 vs. WT and AS-D) whereas Akt activity decreased. The AS-mice, that exhibited a cardiac upregulation of IGF1-R, showed an increase in Akt phosphorylation when diabetic (P<0.05 vs. WT and AS-D). Contrary to WT-D, AS-D hearts did not express inflammatory markers and exhibited a normal capillary density (P<0.05 vs. WT-D)Conclusions: To our knowledge, this is the first study providing new insights into the mechanisms whereby aldosterone prevents diabetes-induced cardiac disorders.
- Subjects
CARDIOTONIC agents; ALDOSTERONE; TYPE 2 diabetes; NEOVASCULARIZATION; CARDIOVASCULAR diseases; LABORATORY mice
- Publication
Cardiovascular Research, 2014, Vol 103, Issue suppl_1, pS110
- ISSN
0008-6363
- Publication type
Article
- DOI
10.1093/cvr/cvu098.39