Alamandine improves cardiac remodeling induced by transverse aortic constriction in mice

Objective: Alamandine is the newest identified peptide of the renin-angiotensin system (RAS) and has protective effects in the cardiovascular system. While it is well known the involvement of classical RAS components in the genesis and progression of cardiac remodelling, less is known about the effects of alamandine. Therefore, in the present study, we investigated the effects of alamandine on cardiac remodelling induced by transverse aortic constriction (TAC) in mice. Methods and results: Male mice (C57BL/6), 10-12 weeks age, were divided in three groups: SHAM, TAC and TAC+ALA (30 µg/kg/day alamandine, for 14 days). The TAC surgery was performed under ketamine and xylazine anesthesia. At the end of treatment, the animals were submitted to echocardiographic examination and subsequently euthanized for tissue collection. TAC induced myocyte hypertrophy, collagen deposition and, the expression of MMP-2 and TGF-b in the left ventricle. These markers of cardiac remodelling were reduced by oral treatment with alamandine. Western blotting analysis showed that alamandine prevents the increase in ERK1/2 phosphorylation, and reverts the decrease in AMPKa phosphorylation induced by TAC. While both TAC and TAC+ALA increased SERCA2 expression, the phosphorylation of phospholambam in Thr17 residue was increased solely in alamandine treated group. The echocardiographic data showed that there are no functional or morphological alterations after two weeks of TAC. Conclusions: Alamandine treatment prevents myocyte hypertrophy and cardiac fibrosis induced by TAC. Our results reinforce the cardioprotective role of alamandine and highlight its therapeutic potential for treating heart diseases related to pressure overload conditions.