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Role of microRNA-146a and its target gene vasorin in the carotid artery remodeling after catheter balloon injury:therapeutic effevt of aerobic physical training

Grant number: 16/26156-5
Support type:Scholarships in Brazil - Master
Effective date (Start): June 01, 2017
Effective date (End): March 31, 2019
Field of knowledge:Health Sciences - Physical Education
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Edilamar Menezes de Oliveira
Grantee:Noemy Pinto Pereira
Home Institution: Escola de Educação Física e Esporte (EEFE). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The Restenosis is a fibroproliferative response that happens on the wall of the blood vessels after an injury, usually followed by the angioplasty procedure, caused by vascular obstruction. The remodeling of the vessel caused by angioplasty is proliferation, growth and migration of smooth muscle cells of media layer for intimal, accompanied by fibrosis, leading in hyperplasia of neointimal and narrowing the vascular lumen. The microRNAs (miRNA) are being widely studied as biomarkers, employed in vascular injury, opening perspectives therapy for the treatment of diseases. The miRNA-146a has gained prominence in fibroproliferative diseases, since it regulates genes involved in this remodeling targets. A modulator of miRNAs expression is physical training (PT), which also has been studied as a non-pharmacological therapy for cardiovascular disease, in which induces various adaptations.So, to test our hypothesis that the PT aerobic changes the miRNA-146a expression and its target gene vasorin in the carotid artery of rats injured with balloon catheter, We use real time PCR to analyze gene expression and Western Blotting to analyze the protein expression of injured carotid artery, and analyze if a repair mechanisms of these vessels occurs through interaction between vasorin and TGF-² pathway, we will see if these mechanisms contribute to the regression of neointimal hyperplasia after vascular injury. For this we will use a PT aerobic protocol (swimming) of moderate intensity and use 4 groups of Wistar rats: Injured with balloon catheter trained (LT), injured (L) and their respective controls. During the trial period will be logged: body weight, blood pressure, resting heart rate and evaluation of the maximum physical effort. After euthanasia, will be dropped for carotid arteries of histology and assess the intima-media thickness. For analysis of citrate synthase, is being removed from skeletal muscle, for validation of aerobic training and will also be carried out analyses of the expression of miRNA-146a and its target gene vasorin and signaling pathway transformation growth factor beta (TGF-²) and its protein expression. (AU)