Voluntary physical activity counteracts Chronic Heart Failure progression affecting both cardiac function and skeletal muscle in the transgenic Tgαq*44 mouse model

Figures

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  Figure 1. In vivo functional performance. Delta of variation of (A) weekly distance of running (km) and (B) weekly time of running (h) between wild‐type (WT) and transgenic (Tg) trained mice. Star marks show significant difference between Tg‐T and age‐matched WT‐T ***P < 0.001. ♦significant different from Tg‐T 6‐mo and 12‐mo P < 0.05; (C) daily mean distance (km) covered by WT and Tg mice before (Pre‐EX) and after (Post‐EX) 2 months of voluntary wheel running at different stages of heart failure. Data are shown as mean ± SD. Star marks show significant difference between Pre‐EX and Post‐EX *P < 0.05 ***P < 0.001. ●significant different from WT Post‐EX 14 months P < 0.05. # significant different from WT Pre‐EX 12 months P < 0.05.

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  Figure 2. MHC isoforms composition. Myosin heavy chain (MHC) isoforms composition in WT‐CTRL, Tg‐CTRL, and Tg‐T groups, at 6, 12, and 14 months of age that correspond to different stages of heart failure. Data are shown as mean ± SD. *P < 0.05, **P < 0.01, ***P < 0.001.

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  Figure 3. Antioxidant defense system. Quantification of (A) SOD1(superoxide dismutase 1) protein level and (B) catalase protein level by western blot analysis (C) proteins carbonylation by Oxyblot analysis in WT‐CTRL, Tg‐CTRL, and Tg‐T mice, at 6, 12, and 14 months of age that correspond to different stages of heart failure. Data are shown as mean ± SD *P < 0.05 **P < 0.01 ***P < 0.001.

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  Figure 4. Protein quality control systems. Quantification of mRNA levels of (A) Atrogin‐1, (B) MuRF‐1 (muscle‐specific ring finger protein‐1) and (D) cathepsin L by RT‐PCR (C) protein level quantification of LC3 (microtubule‐associated protein light chain 3) based on the ratio between the content in forms II and I of LC3 by western blotting in WT‐CTRL, Tg‐CTRL, and Tg‐T mice, at 6, 12, and 14 months of age that correspond to different stages of heart failure. Data are shown as mean ± SD. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.

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  Figure 5. Energetic and oxidative parameters. Quantification of (A) AMPK (AMP‐activated protein kinase) phosphorylation level (B) PGC‐1α (peroxisome proliferative activated receptor‐γ coactivator 1α) protein level (C) DRP1 (dynamin‐related protein 1) protein level (D) Mfn‐1 (mitofusin1) protein level (E) mitochondrial complexes protein levels (I, II, III, IV, V) by western blot analysis in WT‐CTRL, Tg‐CTRL and Tg‐T mice, at 6, 12 and 14 months of age that correspond to different stages of heart failure. The activity level of AMPK was calculated as the ratio between the content in the phosphorylated (p‐form) and total form. Data are shown as mean ± SD. *P < 0.05 **P < 0.01 ***P < 0.001 ****P < 0.0001.