Department of Cardiology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
Eur J Heart Fail. 2022 Feb;24(2):287-298. doi: 10.1002/ejhf.2407. Epub 2022 Jan 9.
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.
运动能力受损是心力衰竭（HF）的关键症状，与生活质量降低和死亡率升高有关。不幸的是，尽管目前的治疗方法通常可以挽救生命，但对运动能力的改善效果很小或微不足道。缓解运动不耐受的特定策略可以改善生活质量，同时可能改善预后。有大量证据表明，体育锻炼可以改善健康和疾病中的心脏和骨骼肌的性能。揭示运动引起的肌肉功能改善的机制基础可以提供靶点，使我们能够提高 HF 中的运动表现。通过本次综述，我们讨论了：（i）最近发现的控制生理性肌肉生长的信号通路以及基础代谢适应运动的线粒体质量控制机制；（ii）HF 中运动不耐受的机制基础以及运动对 HF 患者在分子、功能和预后水平上的益处；（iii）改善 HF 中运动表现的潜在分子疗法。我们提出，在 HF 中促进适应性肌肉生长和线粒体质量控制的新型分子疗法应始终与某种形式的运动训练相结合。
