cardiovascular-agents and alamandine

Thirty years ago, a novel axis of the renin-angiotensin system (RAS) was unveiled by the discovery of angiotensin-(1-7) [ANG-(1-7)] generation in vivo. Later, angiotensin-converting enzyme 2 (ACE2) was shown to be the main mediator of this reaction, and Mas was found to be the receptor for the heptapeptide. The functional analysis of this novel axis of the RAS that followed its discovery revealed numerous protective actions in particular for cardiovascular diseases. In parallel, similar protective actions were also described for one of the two receptors of ANG II, the ANG II type 2 receptor (AT

Topics: Angiotensin I; Angiotensin-Converting Enzyme 2; Animals; Cardiovascular Agents; Cardiovascular Diseases; Cardiovascular System; Congresses as Topic; Humans; Oligopeptides; Peptide Fragments; Peptidyl-Dipeptidase A; Receptor, Angiotensin, Type 2; Receptors, G-Protein-Coupled; Renin-Angiotensin System; Signal Transduction

Alamandine is the newest identified peptide of the renin-angiotensin system (RAS) and has protective effects in the cardiovascular system. Although the involvement of classical RAS components in the genesis and progression of cardiac remodeling is well known, less is known about the effects of alamandine. Therefore, in the present study we investigated the effects of alamandine on cardiac remodeling induced by transverse aortic constriction (TAC) in mice. Male mice (C57BL/6), 10-12 wk of age, were divided into three groups: sham operated, 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 matrix metalloproteinase (MMP)-2 and transforming growth factor (TGF)-β in the left ventricle. These markers of cardiac remodeling 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 5'-adenosine monophosphate-activated protein kinase (AMPK)α phosphorylation induced by TAC. Although both TAC and TAC + ALA increased SERCA2 expression, the phosphorylation of phospholamban in the Thr17 residue was increased solely in the alamandine-treated group. The echocardiographic data showed that there are no functional or morphological alterations after 2 wk of TAC. 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.

Topics: AMP-Activated Protein Kinases; Animals; Aorta; Calcium-Binding Proteins; Cardiovascular Agents; Collagen; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; Heart Ventricles; Hypertrophy, Left Ventricular; Ligation; Male; Matrix Metalloproteinase 2; Mice, Inbred C57BL; Oligopeptides; Oxidative Stress; Phosphorylation; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Signal Transduction; Transforming Growth Factor beta; Ventricular Function, Left; Ventricular Remodeling