MicroRNAs expression in the thoracic aorta of normotensive rats submitted to physical training: perspectives for identifying therapeutic targets related to hypertension.

Abstract

Considering that hypertension is a major public health problem and demand studies for understanding the molecular mechanisms involved in the physiological changes resulting from it, that physical training is important non-pharmacological therapy for hypertensive patients, that gene therapy from microRNAs represent large therapeutic perspectives in controlling blood pressure, and that animal studies are an important tool to complement experimental studies in humans, our proposal is to study the expression of microRNAs in the thoracic aorta of normotensive rats subjected to different amounts of aerobic exercise, compare the results with the expression of microRNAs of the thoracic aorta of spontaneously hypertensive rats, and then select one of the differentially expressed microRNAs by physical training to be modulated in cell culture. Wistar rats 3 months old are will be used at the start of the experiment, divided into three experimental groups (n = 7/group); 1) Not trained, 2) Trained with protocol 1 (T1): 5x/semana/10semanas with overload 5% of body weight, 3) Trained with protocol 2 (T2): T1 even for 8 weeks, 9th week, training 2x/day and 10th week, training 3x/day. Adult spontaneously hypertensive rats (n = 8) will be used to identify the profile of microRNAs of the thoracic aorta and compare them with the profile determined in the aorta of other groups. Throughout the experimental period will be made the following assessments in trained and non-trained rats: records of body weight, evaluation of maximum physical exertion, oxygen consumption, blood pressure and resting heart rate. The animals are sacrificed at the end of the experimental period and will be analyzed the expression of microRNAs of the thoracic aorta of rats using microRNA array. The functionality of the oligonucleotide (anti-miR or miR-Mimic), as well as its ability to stimulate cellular protection against the angiotensin II, will be analyzed in cultured endothelial cells from thoracic aorta of rat.