Alamandine improves cardiac remodeling induced by transverse aortic constriction in mice
| Autor: | Thaís Cristina de Alcântara-Leonídio, Silvia Guatimosim, Itamar Couto Guedes de Jesus, Maria Aparecida Ribeiro Vieira, Robson A.S. Santos, Bruno de Lima Sanches, Rafaela F. da Silva, Mário Morais Silva, Fernando Pedro de Souza-Neto, Gleisy Kelly Goncalves, Melissa de Carvalho Santuchi, Marcos B. Melo |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Alamandine medicine.medical_specialty Physiology Heart Ventricles AMP-Activated Protein Kinases Ventricular Function Left Sarcoplasmic Reticulum Calcium-Transporting ATPases Transforming Growth Factor beta Physiology (medical) Internal medicine Renin–angiotensin system Animals Medicine Phosphorylation Extracellular Signal-Regulated MAP Kinases Ligation Beneficial effects Aorta Ventricular Remodeling business.industry Aortic constriction Calcium-Binding Proteins Cardiovascular Agents Mice Inbred C57BL Disease Models Animal Oxidative Stress Cardiac hypertrophy Cardiology Matrix Metalloproteinase 2 Hypertrophy Left Ventricular Collagen Cardiology and Cardiovascular Medicine business Oligopeptides Signal Transduction |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 320:H352-H363 |
| ISSN: | 1522-1539 0363-6135 |
| DOI: | 10.1152/ajpheart.00328.2020 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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