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Swimming exercise training in vascular remodeling of coronary arteries of spontaneously hypertensive rats: effects on the expression of microRNAs and perspective of identifying therapeutic targets.

Grant number: 13/10472-7
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): October 01, 2013
Effective date (End): September 30, 2016
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal researcher:Edilamar Menezes de Oliveira
Grantee:Fernanda Roberta Roque Redondo
Home Institution: Escola de Educação Física e Esporte (EEFE). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:10/50048-1 - Cellular and functional bases of exercise in cardiovascular diseases , AP.TEM

Abstract

Hypertension is a major public health problem that is associated with vascular changes such as vascular remodeling. Exercise training (ET) is widely used both, for prevention and for the treatment of hypertension promoting beneficial vascular effects. More recently a new class of molecules, microRNAs, has been demonstrated as important gene regulators and is considered potential therapeutic targets for various diseases. Therefore, our proposal is to study the expression of microRNAs in the coronary artery of hypertensive rats (SHR) and identify microRNAs that have changed your profile with hypertension and could be modulated with ET. To select a specific microRNA that will be tested as a possible protector of cellular changes that occurs in response to pathological stimuli in cell culture. For this, the study will be divided into two stages: first will be used SHR and WKY rats (3 months old) and SHR submitted to swimming ET (SHR T - 1x day/5x week/ 10 weeks) for likely to detect microRNAs that may be related to vascular remodeling of coronary arteries. In this step will be performed the control of blood pressure, heart rate and cardiovascular assessment of the animals, in addition to the study of the arterial structure, the microRNAs expression, and the expression of its target genes in the coronary artery. The second stage of this project aims to test the hypothesis that the selected microRNA can be used to prevent cellular alterations induced by one pathological stimulus (angiotensin II). For this, experiments will be carried out in cell cultures of vascular smooth muscle cell (VSMC) of coronary artery from humans. The VSMC will be previously transfected with antagomirs or miR-mimics (depending on the pattern of miRNA expression selected for the study), or an oligonucleotide incompatible with the miRNA studied as controls (scrambler). Then, will be analyze the cell viability and the contraction, proliferation, migration and apoptosis of VSMC, and gene expression of selected miRNA and its target genes that may be related to vascular remodeling. This study will test the hypothesis that the ET can modulate miRNAs that contribute to the vascular remodeling process, which could be further used as a therapeutic source for hypertension.