Acute myocardial infarction (AMI) is a severe cardiovascular disease with high mortality. It is reported to be closely related to the mitochondrial dysfunction and metabolic disturbance on endothelial cells under a chronic hypoxic state. Significant declined mitochondrial respiration, ATP production, and metabolic changes are the main characteristics of endothelial injury in the disease. Trelagliptin is a DPP-4 inhibitor applied for the treatment of type II diabetes and has been recently reported to exert various pharmacological properties. In this investigation, we examined whether Trelagliptin possessed a protective effect against mitochondrial dysfunction and metabolic disturbance in human aortic valvular endothelial cells (HAVECs) under oxygen–glucose deprivation/reperfusion (OGD/R) conditions. We found that both the cytotoxicity and mitochondrial oxidative stress in HAVECs induced by OGD/R stimulation were greatly alleviated by Trelagliptin. In addition, the declined mitochondrial respiration and ATP production decreased secretion of cystathionine and creatine, and the increased production of triglyceride and adiponectin in OGD/R-challenged HAVECs was dramatically reversed by Trelagliptin, accompanied by the upregulated expression level of PGC-1α and CPT-1. Lastly, the AMPK pathway was observed to be significantly activated in OGD/R-challenged HAVECs by Trelagliptin treatment. After co-administration of the inhibitor of the AMPK pathway, the effects of Trelagliptin on mitochondrial function and metabolic alterations were significantly abolished. Taken together, our data indicate that Trelagliptin ameliorated OGD/R-induced mitochondrial disturbance and metabolic changes by activating the AMPK pathway.

急性心肌梗死（AMI）是一种严重的心血管疾病，死亡率很高。据报道，它与慢性缺氧状态下内皮细胞的线粒体功能障碍和代谢紊乱密切相关。线粒体呼吸、ATP产生和代谢变化显着下降是该病内皮损伤的主要特征。曲格列汀是一种用于治疗 II 型糖尿病的 DPP-4 抑制剂，最近有报道称其具有多种药理特性。在这项研究中，我们检查了在氧-葡萄糖剥夺/再灌注 (OGD/R) 条件下，曲格列汀是否对人主动脉瓣内皮细胞 (HAVEC) 中的线粒体功能障碍和代谢紊乱具有保护作用。我们发现曲格列汀极大地减轻了由 OGD/R 刺激诱导的 HAVECs 中的细胞毒性和线粒体氧化应激。此外，线粒体呼吸下降和 ATP 产生减少了胱硫醚和肌酸的分泌，而 OGD/R 攻击的 HAVECs 中甘油三酯和脂联素的产生增加被曲格列汀显着逆转，伴随着 PGC-1α 和 CPT 的表达水平上调-1。最后，观察到 AMPK 通路在 OGD/R 攻击的 HAVEC 中被曲格列汀治疗显着激活。在共同给药 AMPK 通路抑制剂后，曲格列汀对线粒体功能和代谢改变的影响显着消除。综合起来，