Angiotensin II Promotes Skeletal Muscle Angiogenesis Induced by Volume-Dependent Aerobic Exercise Training: Effects on miRNAs-27a/b and Oxidant–Antioxidant Balance

Abstract

Aerobic exercise training (ET) produces beneficial adaptations in skeletal muscles, including angiogenesis. The renin–angiotensin system (RAS) is highly involved in angiogenesis stimuli. However, the molecular mechanisms underlying capillary growth in skeletal muscle induced by aerobic ET are not completely understood. This study aimed to investigate the effects of volume-dependent aerobic ET on skeletal muscle angiogenesis involving the expression of miRNAs-27a and 27b on RAS and oxidant–antioxidant balance. Eight-week-old female Wistar rats were divided into three groups: sedentary control (SC), trained protocol 1 (P1), and trained protocol 2 (P2). P1 consisted of 60 min/day of swimming, 5×/week, for 10 weeks. P2 consisted of the same protocol as P1 until the 8th week, but in the 9th week, rats trained 2×/day, and in the 10th week, trained 3×/day. Angiogenesis and molecular analyses were performed in soleus muscle samples. Furthermore, to establish ET-induced angiogenesis through RAS, animals were treated with an AT1 receptor blocker (losartan). Aerobic ET promoted higher VO2 peak and exercise tolerance values. In contrast, miRNA-27a and -27b levels were reduced in both trained groups, compared with the SC group. This was in parallel with an increase in the ACE1/Ang II/VEGF axis, which led to a higher capillary-to-fiber ratio. Moreover, aerobic ET induced an antioxidant profile increasing skeletal muscle SOD2 and catalase gene expression, which was accompanied by high nitrite levels and reduced nitrotyrosine concentrations in the circulation. Additionally, losartan treatment partially re-established the miRNAs expression and the capillary-to-fiber ratio in the trained groups. In summary, aerobic ET promoted angiogenesis through the miRNA-27a/b–ACE1/Ang II/VEGF axis and improved the redox balance. Losartan treatment demonstrates the participation of RAS in ET-induced vascular growth. miRNAs and RAS components are promising potential targets to modulate angiogenesis for combating vascular diseases, as well as potential biomarkers to monitor training interventions and physical performance.

Post-translational dysregulation of glucose uptake during exhaustive cycling exercise in vastus lateralis muscle of healthy homozygous carriers of the ACE deletion allele

“…Similarly, the correlation between the phosphorylation level of AKT-S473 and capillary-to-fiber ratio in m. Vastus lateralis is intriguing because the latter reflects of the capacity for insulin-mediated glucose uptake in skeletal muscle ( Hedman et al, 2001 ). AKT-S473 phosphorylation is known with angiogenesis ( Shiojima and Walsh 2002 ) and high angiotensin 2 levels are associated with exercise-induced skeletal muscle angiogenesis in laboratory models (reviewed in Rodrigues et al, 2022 ). As well, we observed a trend for a negative correlation between the phosphorylation of AKT-S473 and COX4I1 transcript levels in m. Vastus lateralis ( Table 5 ) which relate to the recently reported association between AKT-S473 expression and phosphorylation and the protein expression of cytochrome C oxidative subunits in mouse skeletal muscle ( Jaiswal et al, 2022 ).…”

Mitigation of Subsequent Ovariectomy Responses through Prior Exercise Training in Rats

“…Muscle cross-sectional area (CSA) Soleus muscle was chosen for the analysis because it has a predominance of oxidative fibers and a previous study has demonstrated the ability of this muscle to adjust to the exercise, mainly in terms of functionality [18]. Soleus muscle was carefully harvested, snapfrozen in isopentane and stored in liquid nitrogen.…”

Efeito do treinamento físico aeróbio na miopatia muscular esquelética induzida pela insuficiência cardíaca: participação dos microRNA\'s no perfil de fibras

“…Dados prévios do nosso laboratório corroboram com os da literatura na tentativa de explicar os efeitos benéficos do TFA sobre a expressão de miRNAs na modulação de genes relacionados com a musculatura esquelética e o sistema cardiovascular (FERNANDES et al, 2015;PEREIRA et al, 2020;PELOZIN et al, 2022;RODRIGUES et al, 2022). Entretanto, entendemos que o próximo passo seria relacioná-lo de forma direta às alterações músculo esquelético induzida pela IC; haja visto que, embora de suma importância, pouco se tem publicado a respeito desse contexto sobre miRNA, TFA e DCVs.…”