Transcriptome analysis of skeletal muscles revealed the effect of exercise on the molecular mechanisms regulating muscle growth and metabolism in patients with heart failure

Abstract

Aim. Heart failure (HF) is accompanied by skeletal muscle atrophy and exercise intolerance. The aim was to study the molecular mechanisms underlying the therapeutic effect of personalized exercise in patients with HF.Material and methods. RNA sequencing obtained from skeletal muscle biopsies before and after a 12-week exercise course was used to identify changes in gene expression and signaling pathways induced by the physical rehabilitation program for patients with HF.Results. We have shown that personalized exercise program in patients with HF stimulates the activation of molecular pathways regulating the differentiation and functioning of skeletal muscles: commitment of muscle progenitor cells; mechanisms regulating the calcium release and sensitivity of myofibrillar contraction, electrical excitability of the muscle membrane, synaptic vesicle proton gradient creation, maintenance of electrochemical gradients of Na+ /K+ . Also, the analysis of differentially expressed genes revealed an increase in the expression of transcription factors MyoD and MEF2, which are responsible for the differentiation of muscle stem cells, and sarcomeric genes MYOM1, MYOM2, MYH7. Along with this, we observed activation of the CYR61 expression — a potential prognostic biomarker for HF patients.Conclusion. Our data show that the beneficial effect of personalized aerobic exercise in patients with HF depends, at least in part, on an improvement in the physiological and biochemical parameters of skeletal muscle.