Exercise: a molecular tool to boost muscle growth and mitochondrial performance in heart failure?

Abstract

Impaired exercise capacity is the key symptom of heart failure (HF) and is associated with reduced quality of life and higher mortality rates. Unfortunately, current therapies, although generally lifesaving, have only small or marginal effects on exercise capacity. Specific strategies to alleviate exercise intolerance may improve quality of life, while possibly improving prognosis as well. There is overwhelming evidence that physical exercise improves performance in cardiac and skeletal muscles in health and disease. Unravelling the mechanistic underpinnings of exercise-induced improvements in muscle function could provide targets that will allow us to boost exercise performance in HF. With the current review we discuss: (i) recently discovered signalling pathways that govern physiological muscle growth as well as mitochondrial quality control mechanisms that underlie metabolic adaptations to exercise; (ii) the mechanistic underpinnings of exercise intolerance in HF and the benefits of exercise in HF patients on molecular, functional and prognostic levels; and (iii) potential molecular therapeutics to improve exercise performance in HF. We propose that novel molecular therapies to boost adaptive muscle growth and mitochondrial quality control in HF should always be combined with some form of exercise training.

Could SGLT2 Inhibitors Improve Exercise Intolerance in Chronic Heart Failure?

“…Dynamic mitochondrial processes in the form of fusion, autophagy, and fission are crucial to the vitality and lifespan of mitochondria [ 135 ]. However, in HF mitochondrial dynamics are impaired [ 136 ]. One of the mechanisms responsible for the impediments in mitochondrial dynamics is the increased acetylation of mitochondrial proteins in the failing heart [ 86 , 135 ] as well as in skeletal muscle [ 134 ].…”

February 2022 at a glance: focus on pathophysiology and acute heart failure

“…Nijholt et al . 6 reviewed the most recent findings in the field, focusing on newly discovered pathways associated with muscular growth, mechanisms of exercise intolerance and potential therapeutic options.…”

“…Exercise capacity is impaired in patients with heart failure (HF) with a major impact on their poorer quality of life and frequent hospitalizations. [3][4][5] Nijholt et al 6 reviewed the most recent findings in the field, focusing on newly discovered pathways associated with muscular growth, mechanisms of exercise intolerance and potential therapeutic options.…”

Exercise intolerance in heart failure: beyond mitochondrial dysfunction. Letter regarding the article ‘Exercise: a molecular tool to boost muscle growth and mitochondrial performance in heart failure?’

“…The recent review about the potential role and benefits of exercise training in signalling pathways regulation, mitochondrial biogenesis and bioenergetics has primarily focused on decremental effects of mitochondrial dysfunction on aerobic exercise intolerance in heart failure (HF). 1 For clinicians, however, it is also important to be aware of other exerciselimiting factors, such as iron deficiency 2 and (hyper)activity of autonomic nervous system during aerobic and resistance training. 3 Iron deficiency is highly prevalent in patients with stable HF and it is associated with progression and worsening of the syndrome, poor quality of life and exercise capacity, which is independent of haemoglobin levels.…”