Cardiovascular Research Center, Corrigan Minehan Heart Center, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Boston, MA, 02129, USA.
Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Curr Heart Fail Rep. 2022 Aug;19(4):180-190. doi: 10.1007/s11897-022-00554-1. Epub 2022 May 14.
We review the clinical benefits of altering myocardial substrate metabolism in heart failure.
Modulation of cardiac substrates (fatty acid, glucose, or ketone metabolism) offers a wide range of therapeutic possibilities which may be applicable to heart failure. Augmenting ketone oxidation seems to offer great promise as a new therapeutic modality in heart failure. The heart has long been recognized as metabolic omnivore, meaning it can utilize a variety of energy substrates to maintain adequate ATP production. The adult heart uses fatty acid as a major fuel source, but it can also derive energy from other substrates including glucose and ketone, and to some extent pyruvate, lactate, and amino acids. However, cardiomyocytes of the failing heart endure remarkable metabolic remodeling including a shift in substrate utilization and reduced ATP production, which account for cardiac remodeling and dysfunction. Research to understand the implication of myocardial metabolic perturbation in heart failure has grown in recent years, and this has raised interest in targeting myocardial substrate metabolism for heart failure therapy. Due to the interdependency between different pathways, the main therapeutic metabolic approaches include inhibiting fatty acid uptake/fatty acid oxidation, reducing circulating fatty acid levels, increasing glucose oxidation, and augmenting ketone oxidation.
我们综述了改变心力衰竭中心肌代谢底物的临床获益。
心脏底物（脂肪酸、葡萄糖或酮代谢）的调节提供了广泛的治疗可能性，可能适用于心力衰竭。增强酮氧化似乎为心力衰竭的一种新的治疗方式提供了巨大的希望。心脏长期以来被认为是代谢杂食动物，这意味着它可以利用多种能量底物来维持足够的 ATP 生成。成人心脏主要以脂肪酸作为燃料来源，但它也可以从其他底物中获取能量，包括葡萄糖和酮，在某种程度上还包括丙酮酸、乳酸和氨基酸。然而，衰竭心脏的心肌经历了显著的代谢重塑，包括底物利用的转变和 ATP 生成的减少，这是导致心脏重塑和功能障碍的原因。近年来，研究理解心肌代谢紊乱对心力衰竭的影响有了很大的进展，这增加了人们对心力衰竭治疗靶向心肌代谢底物的兴趣。由于不同途径的相互依存性，主要的治疗代谢方法包括抑制脂肪酸摄取/脂肪酸氧化、降低循环脂肪酸水平、增加葡萄糖氧化和增强酮氧化。
