Karwi Qutuba G, Lopaschuk Gary D
Cardiovascular Research Centre, University of Alberta, Edmonton, AB, T6G 2S2, Canada.
Department of Pharmacology, College of Medicine, University of Diyala, Diyala, Iraq.
Cardiovasc Drugs Ther. 2023 Apr;37(2):413-420. doi: 10.1007/s10557-022-07320-4. Epub 2022 Feb 12.
Branched-chain amino acids (BCAAs) are essential amino acids which have critical roles in protein synthesis and energy metabolism in the body. In the heart, there is a strong correlation between impaired BCAA oxidation and contractile dysfunction in heart failure. Plasma and myocardial levels of BCAA and their metabolites, namely branched-chain keto acids (BCKAs), are also linked to cardiac insulin resistance and worsening adverse remodelling in the failing heart. This review discusses the regulation of BCAA metabolism in the heart and the impact of depressed cardiac BCAA oxidation on cardiac energy metabolism, function, and structure in heart failure. While impaired BCAA oxidation in the failing heart causes the accumulation of BCAA and BCKA in the myocardium, recent evidence suggested that the BCAAs and BCKAs have divergent effects on the insulin signalling pathway and the mammalian target of the rapamycin (mTOR) signalling pathway. Dietary and pharmacological interventions that enhance cardiac BCAA oxidation and limit the accumulation of cardiac BCAAs and BCKAs have been shown to have cardioprotective effects in the setting of ischemic heart disease and heart failure. Thus, targeting cardiac BCAA oxidation may be a promising therapeutic approach for heart failure.
支链氨基酸（BCAAs）是必需氨基酸，在人体蛋白质合成和能量代谢中发挥着关键作用。在心脏中，BCAA氧化受损与心力衰竭时的收缩功能障碍之间存在密切关联。血浆和心肌中的BCAA及其代谢产物，即支链酮酸（BCKAs），也与心脏胰岛素抵抗以及衰竭心脏中不良重塑的加剧有关。本综述讨论了心脏中BCAA代谢的调节以及心脏BCAA氧化降低对心力衰竭时心脏能量代谢、功能和结构的影响。虽然衰竭心脏中BCAA氧化受损会导致心肌中BCAA和BCKA的积累，但最近的证据表明，BCAAs和BCKAs对胰岛素信号通路和雷帕霉素哺乳动物靶点（mTOR）信号通路具有不同的影响。在缺血性心脏病和心力衰竭的情况下，增强心脏BCAA氧化并限制心脏BCAAs和BCKAs积累的饮食和药物干预已显示出具有心脏保护作用。因此，针对心脏BCAA氧化可能是一种有前景的心力衰竭治疗方法。
