Abstract

Coronary no-reflow damage is caused by endothelial cell damage although little drug is available to intervene in coronary no-reflow. Liraglutide is a kind of anti-diabetic drug and its cardioprotective role has been widely reported. In this study, we explored the role of liraglutide in regulating coronary endothelial cell damage. We used hydrogen peroxide to mimic coronary no-reflow damage in vitro. After exposure to hydrogen peroxide, endothelial cells’ viability was significantly reduced, an effect that was followed by an increase in cell apoptosis. Interestingly, liraglutide treatment obviously upregulated endothelial cell viability and thus prevented cell apoptosis. Further, we also found that liraglutide inhibited the activation of caspase-3 in hydrogen peroxide-treated endothelial cells. Besides, cellular metabolism, as reflected by mitochondrial membrane potential, was disrupted by hydrogen peroxide and reversed to normal levels with liraglutide. Further, we found that the ERK pathway is a potential downstream effector of liraglutide. Administration of liraglutide significantly promoted the activation of ERK and this effect may contribute to endothelial cell survival. Altogether, our results illustrated that hydrogen peroxide-mediated endothelial cell damage could be attenuated by liraglutide through modulation of the MAPK/ERK signaling pathway. This finding will pave a novel road for the intervention of coronary no-reflow damage in patients suffering from myocardial infarction.

摘要

冠状动脉无复流损伤是由内皮细胞损伤引起的，尽管很少有药物可用于干预冠状动脉无复流。利拉鲁肽是一种抗糖尿病药物，其心脏保护作用已被广泛报道。在本研究中，我们探讨了利拉鲁肽在调节冠状动脉内皮细胞损伤中的作用。我们使用过氧化氢在体外模拟冠状动脉无复流损伤. 暴露于过氧化氢后，内皮细胞的活力显着降低，随后细胞凋亡增加。有趣的是，利拉鲁肽治疗明显上调内皮细胞活力，从而阻止细胞凋亡。此外，我们还发现利拉鲁肽抑制过氧化氢处理的内皮细胞中 caspase-3 的活化。此外，细胞代谢，如线粒体膜电位所反映的，被过氧化氢破坏，而利拉鲁肽则逆转至正常水平。此外，我们发现 ERK 通路是利拉鲁肽的潜在下游效应器。利拉鲁肽的给药显着促进了 ERK 的激活，这种作用可能有助于内皮细胞的存活。共，我们的研究结果表明，利拉鲁肽可通过调节 MAPK/ERK 信号通路减轻过氧化氢介导的内皮细胞损伤。这一发现将为心肌梗死患者冠状动脉无复流损伤的干预开辟一条新道路。