Efeitos da alamandina no remodelamento vascular induzido pela constrição da aorta transversa em camundongos

Abstract

Introduction The peptide alamandine has been recently discovered and characterized as the newest component from the renin angiotensin system. So far, alamandine is derived from the catalytic action of ECA2 over Angiotensin A and from,the descarboxylation of Angiotensin-(1-7). Through the interaction with its receptor, MrgD, alamandine has shown to have protective effects to the cardiovascular system. It is well established the participation of certain components of the classic renin angiotensin system in vascular diseases characterized by arterial remodeling. However, there is no knowledge about the effects of alamandine in the animal model of transverse aortic constriction-induced vascular remodeling. Aim To evaluate the effects of alamandine on mice ascending aorta remodeling after transverse aortic constriction.Materials and Methods We used C57BL/6 male mice (20-25g) from 1012 weeks age (CEUA 349/2016). The animals were splited into the following groups: Sham (false operated), TAC (operated) and TAC+ALA (operated and treated with alamandine, 30 µg/kg/day, by gavage). After a period of 14 days of treatment, the animals were euthanized and the ascending aorta was collected. The results show that oral administration of alamandine attenuated the remodeling in the ascending aorta induced by TAC, as well as reduced the fibrosis, the gelatinolytic activity of the matrix metalloproteinases (MMPs) and the expression of MMP-2. The results also demonstrate that alamandine decreased the production of reactive oxygen species and the gene expression of proinflammatory cytokines. Furthermore, treatment with alamandine also modulated the protein expression of MrgD receptor and reduced the increase of gene expression of AT1 receptor-induced by TAC. Conclusions Our results demonstrate that alamandine treatment reduces the vascular remodeling after TAC through anti-fibrotic, anti-oxidant and anti-inflammatory effects. Hence, this work opens new avenues for the use of alamandine as a promising therapeutic target in cardiovascular diseases.