Effect of exercise training on skeletal muscle and myocardial transcriptomics and function in experimental heart failure
B H Wang, R Magaye, D Henstridage, H Kiriazis, L Shan, Fumi Takeuchi, W Ho, E J Howden, D M KayeAbstract
Background
Exercise training is an evidence-based adjunctive treatment for patients with heart failure (HF). However, the mechanisms by which exercise improves muscular and cardiac function have not been comprehensively explored. This study aims to uncover these mechanisms using a transgenic (Tg) mouse model of HF and to provide further evidence of the beneficial effects of exercise in the HF setting.
Materials and methods
10-week-old male Mst1 Tg mice with HF and male littermate non-Tg controls (10 weeks old) underwent structured exercise training for 6 weeks or normal activity. At the end of the study, skeletal muscle and heart tissue were collected for histology, RNA sequencing, and gene expression analyses to explore mechanisms and the transcriptomic profile. Echocardiography was used to confirm cardiac dysfunction.
Results
HF was associated with substantial alterations in the skeletal muscle transcriptome, including downregulation of pathways related to aerobic metabolism, electron transport, and the TCA cycle, together with upregulation of inflammatory pathways related to cytokines and T cells. Exercise training improved exercise capacity in DCM mice over time and enriched metabolic pathways in skeletal muscle, consistent with a recovery of slow-twitch fiber type. Within the myocardium, exercise training reduced ventricular wall thickness and myocardial fibrosis, with improvements in systemic blood pressure.
Conclusions
This study demonstrated significant beneficial effects of exercise on the muscular transcriptomic profile, with improved exercise capacity in a Tg mouse model of HF. These beneficial effects are at least in part due to increased muscular endurance and reduced skeletal muscle fibrosis.