Spontaneously hypertensive rats develop left ventricular hypertrophy, increased blood pressure and blood pressure variability, which are important determinants of heart damage, like the activation of renin-angiotensin system.

Overactivation of the classical arm of the renin-angiotensin (Ang) system (RAS) occurs during inflammation, oxidative stress and obesity-induced cardiomyopathy. The activation of the protective arm of RAS may act to counterbalance the deleterious effects of the classical RAS. Although aerobic exercise training (AET) shifts the balance of the RAS towards the protective arm, little is known about the molecular adaptations to different volumes of AET. The aim of this study was to evaluate the impact of AET volume on the modulation of RAS, as well as on cardiac biomarkers of oxidative stress and inflammation, in a diet-induced obesity model. Male Wistar rats were fed either control (CON) or high fat (HF) diet for 32 weeks. At week 20, HF group was subdivided into sedentary, low (LEV, 150 min/week) or high (HEV, 300 min/week) exercise volume. After 12 weeks of exercise, body mass gain, systolic blood pressure and heart rate were evaluated, as well as RAS, oxidative stress and inflammation in the heart. Body mass gain, systolic blood pressure and heart rate were higher in HF group when compared with SC group. Both trained groups restored systolic blood pressure and heart rate, but only HEV reduced body mass gain. Regarding the cardiac RAS, the HF group exhibited favoring of the classical arm and both trained groups shifted the balance towards the counterregulatory protective arm. The HF group had higher B1R expression and lower B2R expression than the control group, and B2R expression was reverted in both trained groups. The HF group also presented oxidative stress. The LEV and HEV groups improved the cardiac redox status by reducing Nox 2 and nitrotyrosine expression, but only the LEV group was able to increase the antioxidant defense by increasing Nrf2 signaling. While the HF group presented higher TNF-α, IL-6 and NFκB expression, and lower IL-10 expression, than the SC group, both training protocols improved the inflammatory profile. Although both trained groups improved the deleterious changes related to obesity cardiomyopathy, it is clear that the molecular mechanisms differ between them. Our results suggest that different exercise volumes might reach different molecular targets, and this could be a relevant factor when using exercise to manage obesity.

We investigated the effects of AET on myomiRs expression in the skeletal muscle and serum of colon cachectic (CT26) and breast non-cachectic (MMTV-PyMT) cancer mice models. Colon cancer decreased microRNA-486 expression, increasing PTEN in tibialis anterior muscle (TA), decreasing the PI3K/mTOR protein pathway, body and muscle wasting, fibers' cross-sectional area and muscle dysfunction, that were not preserved by AET. In contrast, breast cancer decreased those muscle functions, but were preserved by AET. In circulation, the downregulation of microRNA-486 and -206 in colon cancer, and the downregulation of microRNA-486 and upregulation of microRNA-206 expression in breast cancer might be good cancer serum biomarkers. Since the microRNA-206 is skeletal muscle specific, their expression was increased in the TA, serum and tumor in MMTV, suggesting a communication among these three compartments. The AET prevents these effects on microRNA-206, but not on microRNA-486 in MMTV. In conclusion, cancer induced a downregulation of microRNA-486 expression in TA and serum of CT26 and MMTV mice and these effects were not prevented by AET; however, to MMTV, the trained muscle function was preserved, probably sustained by the downregulation of microRNA-206 expression. Serum microRNA-206 is a potential biomarker for colon (decreased) and breast (increased) cancer to monitor the disease evolution and the effects promoted by the AET.

Obesity and renin angiotensin system (RAS) hyperactivity are profoundly involved in cardiovascular diseases, however aerobic exercise training (EXT) can prevent obesity and cardiac RAS activation. The study hypothesis was to investigate whether obesity and its association with EXT alter the systemic and cardiac RAS components in an obese Zucker rat strain.

Impaired cardiomyocyte contractility and calcium handling are hallmarks of left ventricular contractile dysfunction. Exercise training has been used as a remarkable strategy in the treatment of heart disease. The microRNA-1, which targets sodium/calcium exchanger 1 (NCX), and microRNA-214, which targets sarcoplasmic reticulum calcium ATPase-2a (Serca2a), are involved in cardiac function regulation. Thus, the aim of this study was to evaluate the effect of exercise training on cardiac microRNA-1 and -214 expression after myocardial infarction.

To investigate the role of physical activity in functional and molecular bladder alterations in an obese and insulin-resistant murine model.

Exercise training (ET) has been established as an important treatment for obesity, since it counteracts aberrant cardiac metabolism and weight gain; however, underlying mechanisms remain to be further determined. MicroRNAs (miRNAs) inhibit protein expression by base-pairing with the 3' UTRs of mRNA targets. MiRNA-208a is a cardiac-specific miRNA that regulates β-MHC content and systemic energy homeostasis via MED13. We investigated whether ET regulates the cardiac miRNA-208a and its target MED13, reducing the weight gain and β-MHC expression in obese Zucker rats (OZR). OZR (n = 11) and Lean (L, n = 10) male rats were assigned into 4 groups: OZR, trained OZR (OZRT), L and trained L (LT). Swimming ET consisted of 60 min of duration, 1x/day, 5x/week/10 weeks. MiRNA and gene expression were analyzed by real-time PCR and protein levels by western blot. Resting bradycardia was observed in trained groups. ET reduced weight gain, retroperitoneal fat weight and adipocyte cell size in OZRT compared with OZR group. Cardiac miRNA-208a levels increased 57% in OZR paralleled with a decrease of 39% in MED13 protein levels compared with L group. In contrast, ET corrected the cardiac miRNA-208a and MED13 levels in OZRT compared with L group. Furthermore, ET reduced the increased cardiac mass and normalized β-MHC protein levels caused by obesity. These results suggest that ET can prevent weight gain and pathological cardiac hypertrophy via increased of cardiac MED13 by the regulation of miRNA-208a. Therefore, miRNA-208a can be used as potential therapeutic target for metabolic and cardiac disorders.

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.