William Harvey Research Institute, Centre for Biochemical Pharmacology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, UK.
School of Cardiovascular Medicine and Sciences, British Heart Foundation Centre of Research Excellence, King's College London, The Rayne Institute, St Thomas' Hospital, London, UK.
J Mol Cell Cardiol. 2021 Dec;161:106-115. doi: 10.1016/j.yjmcc.2021.08.003. Epub 2021 Aug 8.
Elevated intracellular Na (Na) and metabolic impairment are interrelated pathophysiological features of the failing heart (HF). There have been a number of studies showing that myocardial sodium elevation subtly affects mitochondrial function. During contraction, mitochondrial calcium (Ca) stimulates a variety of TCA cycle enzymes, thereby providing reducing equivalents to maintain ATP supply. Na elevation has been shown to impact Ca; however, whether metabolic remodelling in HF is caused by increased Na has only been recently demonstrated. This novel insight may help to elucidate the contribution of metabolic remodelling in the pathophysiology of HF, the lack of efficacy of current HF therapies and a rationale for the development of future metabolism-targeting treatments. Here we review the relationship between Na pump inhibition, elevated Na, and altered metabolic profile in the context of HF and their link to metabolic (in)flexibility and mitochondrial reprogramming.
细胞内钠离子（Na）浓度升高和代谢损伤是心力衰竭（HF）的相关病理生理特征。有多项研究表明，心肌钠离子浓度升高会轻微影响线粒体功能。在收缩过程中，线粒体钙离子（Ca）刺激多种三羧酸循环酶，从而提供还原当量以维持 ATP 供应。已有研究表明 Na 浓度升高会影响 Ca；然而，HF 中的代谢重塑是否由 Na 浓度升高引起，最近才得到证实。这一新的认识可能有助于阐明代谢重塑在 HF 病理生理学中的作用、目前 HF 治疗方法缺乏疗效的原因，以及为未来针对代谢的治疗方法提供理论依据。本文综述了 HF 中钠泵抑制、Na 浓度升高和代谢特征改变之间的关系，以及它们与代谢（不）灵活性和线粒体重编程的联系。
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