King N
School of Biomedical Science, Faculty of Health, University of Plymouth, Plymouth, PL4 8AA, England, UK.
Amino Acids. 2025 Oct 22;57(1):52. doi: 10.1007/s00726-025-03485-y.
Stopping then restarting the blood flow to the heart can cause ischaemia reperfusion (IR) injury. This can happen during revascularisation following a myocardial infarction and during on pump cardiac surgery using cardioplegic arrest. Despite extensive studies to identify cardioprotective interventions, the myocardium continues to sustain significant injury. Therefore, there is a need to identify agents that can be used during IR. This review focuses on the potential cardioprotective role for acidic amino acids and natural dipeptides using evidence from experimental studies and clinical trials with particular emphasis on their membrane transport. Acidic amino acids are present at high concentration in the heart with a large tissue to plasma concentration gradient, where they are involved in protein synthesis and intermediary metabolism. During cardiac insults they are lost from heart cells but replenishment leads to cardioprotection through energy provision, protection against the production of reactive oxygen species production and improved calcium homeostasis. One important determinant of the intracellular concentration of acidic amino acids and natural dipeptides is membrane transport. The expression and activity of the acidic amino acids transporters EAAT1-3 and the dipeptide transporter, PEPT2 have been demonstrated in membrane vesicles and isolated cardiomyocytes. Improvements in our understanding of these different transport mechanisms should lead to the maximisation of acidic amino acid and natural dipeptide uptake during IR leading to improved cardioprotection.
阻断然后重新恢复心脏的血流会导致缺血再灌注（IR）损伤。这可能发生在心肌梗死后的血管重建过程中以及使用心脏停搏液的体外循环心脏手术期间。尽管进行了大量研究以确定心脏保护干预措施，但心肌仍持续遭受严重损伤。因此，有必要确定在缺血再灌注期间可使用的药物。本综述利用实验研究和临床试验的证据，重点关注酸性氨基酸和天然二肽的潜在心脏保护作用，特别强调它们的膜转运。酸性氨基酸在心脏中以高浓度存在，组织与血浆浓度梯度很大，它们参与蛋白质合成和中间代谢。在心脏损伤期间，它们从心脏细胞中丢失，但补充可通过提供能量、防止活性氧产生以及改善钙稳态来实现心脏保护。酸性氨基酸和天然二肽细胞内浓度的一个重要决定因素是膜转运。酸性氨基酸转运体EAAT1 - 3和二肽转运体PEPT2的表达和活性已在膜囊泡和分离的心肌细胞中得到证实。对这些不同转运机制的理解的改善应能在缺血再灌注期间使酸性氨基酸和天然二肽的摄取最大化，从而增强心脏保护作用。
