Aerobic exercise training (ET) produces beneficial adaptations in skeletal muscle including angiogenesis. The renin-angiotensin system (RAS) is highly involved in angiogenesis stimuli induced by ET. However, the molecular mechanisms underlying capillary growth in skeletal muscle induced by ET are not completed understood. The study aimed to investigate the effects of volume-dependent aerobic ET on skeletal muscle angiogenesis involving the expression of miRNAs-27a/b on RAS and oxidant-antioxidant balance. Eight-week-old female Wistar rats were divided into three groups: sedentary control (SC), trained protocol 1 (P1), trained protocol 2 (P2). P1 consisted of 60 minutes/day of swimming, 5x/week, for 10 weeks. P2 consisted of the same protocol as P1 until the 8th week; in the 9th week, rats trained 2x/day, and in the 10th week, trained 3x/day. Angiogenesis and molecular analysis were evaluated in the soleus muscle. Also, to establish ET-induced angiogenesis through RAS, animals were treated with an AT1 receptor blocker (losartan). Aerobic ET promoted higher values to VO2 peak and exercise tolerance. In contrast, miRNA-27a/b levels were reduced in both trained groups compared to the SC group paralleled by increased of the ACE I-Ang II-VEGF axis, which lead to higher capillary to fiber ratio. Also, aerobic ET induced antioxidant profile increasing skeletal muscle Sod2 and catalase gene expression accompanied by high nitrite levels and reduced nitrotyrosine concentration in the circulation. Additionally, losartan treatment reestablishes partially the miRNAs expression and the capillary to fiber ratio in trained groups. Together, aerobic ET induced angiogenesis through of the ACE I-Ang II-VEGF axis and improved the redox balance. Losartan treatment confirms the participant of RAS on vascular growth induced by ET. It is promising that miRNAs and RAS components may be acted as a potential target to modulate angiogenesis for combating vascular diseases, as well as potential biomarkers to monitor training interventions and physical performance.
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