Combined aerobic and resistance exercise training restores perivascular adipose tissue function in the thoracic aorta of rats with heart failure

Figures

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  Figure 1. Exercise training improves the anticontractile effect of tPVAT and induces browning in heart failure rats. Concentration-response curves to phenylephrine in thoracic aortic rings with (+) and without (−) PVAT from (A) untrained sham-operated (uSO) and training sham-operated (tSO) rats; (B) untrained heart failure (uHF) and training heart failure (tHF) rats; and (C) maximum effect values (Emax) obtained in each condition and group. Gene expression of (D) brown (PRDM-16), (E) beige (EPSTI-1), and (F) white (TCF-21) adipose tissue markers, and (G) UCP1 and (H) mtTFA mitochondrial metabolic and biogenic markers in tPVAT from the studied groups. All results are expressed as mean ± SEM. Gene expression is presented as the fold of induction to the uSO group. A two-way analysis of variance (ANOVA) followed by the Tukey post-hoc test was used to compare the results. *P<0.05 vs. uSO; # P<0.05 vs. uHF; α P<0.05 vs. untrained PVAT−; βP<0.05 vs. trained PVAT−. HPRT-1, hypoxanthine–guanine phosphoribosyl transferase 1.

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  Figure 2. Exercise training enhances NO bioavailability and eNOS gene expression in the tPVAT of heart failure rats. Concentration-response curves to phenylephrine in thoracic aortic rings PVAT+ from (A) untrained sham-operated (uSO); (B) untrained heart failure (uHF); and (C) training heart failure (tHF) rats, previously incubated, or not, with L-NAME (100 μmol/L) for 30 min. (D) Gene expression of eNOS was detected in tPVAT from the studied groups. All results are expressed as mean ± SEM. Gene expression is presented as the fold of induction to the uSO group. A two- or one-way analysis of variance (ANOVA) followed by the Tukey post-hoc test was used to compare the results. *P<0.05 vs. uSO; # P<0.05 vs. uHF; βP<0.05 vs. PVAT+.

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  Figure 3. Exercise training improves the antioxidant and anti-inflammatory profile of tPVAT of heart failure rats. (A) Representative laser-scanning fluorescent micrographs of tPVAT from (A) untrained sham-operated (uSO); (B) untrained heart failure (uHF); and (C) training heart failure (tHF) rats, preloaded with dihydroethidine (DHE) for ROS detection, or 4′,6-diamidino-2-phenylindole (DAPI) for nuclei detection. The histogram showed the mean of fluorescence intensity (% emission/nucleus to the uSO group) of DHE dye in slices of tPVAT from each group. Gene expression of (B) IL-6; (C) TNF-α; (D) MCP-1; and (E) IL-10 detected in tPVAT from studied groups. All results are expressed as mean ± SEM. Gene expression is presented as the fold of induction to the uSO group. One-way analysis of variance (ANOVA) followed by the Tukey post-hoc test was used to compare the results. *P<0.05 vs. uSO; # P<0.05 vs. uHF.

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  Figure 4. The effect of exercise training on tPVAT of heart failure rats involved the noradrenaline pathway but not the angiotensin II system. (A) Angiotensin II levels; (B) protein expression of tyrosine hydroxylase; and (C) noradrenaline levels detected in tPVAT from untrained sham-operated (uSO); untrained heart failure (uHF); and training heart failure (tHF) rats. All results are expressed as mean ± SEM. Ponceau staining was used to normalize the expression of the evaluated protein. One-way analysis of variance (ANOVA) followed by the Tukey post-hoc test was used to compare the results. *P<0.05 vs. uSO; # P<0.05 vs. uHF.

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  Figure 5. The β3-AR/adiponectin/AMPK signaling pathway is involved in the beneficial effect of exercise training in HF rats. (A) Gene expression of the β3-adrenoceptor (AR); (B) adiponectin levels; and (C) pAMPKThr172 to AMPK ratio protein expression in tPVAT from untrained sham-operated (uSO), untrained heart failure (uHF), and trained heart failure (tHF) rats. All results are expressed as mean ± SEM. Gene expression is presented as the fold of induction to the uSO group. One-way analysis of variance (ANOVA) followed by the Tukey post-hoc test was used to compare the results. *P<0.05 vs. uSO; # P<0.05 vs. uHF.

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  Figure 6. Main adjustments found in the tPVAT of untrained and exercise-trained heart failure rats. The image summarizes the main findings observed in tPVAT of untrained (sedentary) and 8-week combined aerobic and resistance-trained heart failure (HF) rats. These findings highlight the potential of exercise training as a non-pharmacological approach to managing PVAT and vascular adjustments in HF. Image created with BioRender.com.