RETRACTED ARTICLE: Protective role of arachidonic acid against diabetic myocardial ischemic injury: a translational study of pigs, rats, and humans

作者：Yunhui Lv, Kai Li, Shuo Wang, Xiaokang Wang, Xiaokang Wang, Guangxin Yue, Yangyang Zhang, Xin Lv, Ping Zhao, Shiping Wang, Qi Zhang, Qiuju Li, Jinyan Zhu, Jubo Li, Peng Peng, Yue Li, Jiafei Luo, Xue Zhang, Jianzhong Yang, Baojie Zhang, Xuemin Wang, Xuemin Wang, Min Zhang, Chen Shen, Xin Wang, Xin Wang, Miao Wang, Zhen Ye, Yongchun Cui · 发表于：Cardiovascular Diabetology · 年份：2024 · DOI：10.1186/s12933-024-02123-3 · 被引用次数：22 · 研究领域：Cardiac Ischemia and Reperfusion、Eicosanoids and Hypertension Pharmacology、Cardiovascular Function and Risk Factors

Abstract Aim Patients with diabetes mellitus have poor prognosis after myocardial ischemic injury. However, the mechanism is unclear and there are no related therapies. We aimed to identify regulators of diabetic myocardial ischemic injury. Methods and results Mass spectrometry-based, non-targeted metabolomic approach was used to profile coronary sinus blood from diabetic and non-diabetic Bama-mini pigs at 0.5-h post coronary artery ligation. Six metabolites had a |log 2 (Fold Change)|> 1.3. Among them, the most changed is arachidonic acid (AA), levels of which were 32 times lower in diabetic pigs than in non-diabetic pigs. The AA-derived products, PGI 2 and 6-keto-PGF 1α , were also significantly reduced. AA treatment of cultured cardiomyocytes protected against cell death by 30% at 48 h of high glucose and oxygen deprivation, which coincided with increased mitophagic activity (as indicated by increased LC3II/LC3I, decreased p62 and increased parkin & PINK1), improved mitochondrial renewal (upregulation of Drp1 and FIS1), reduced ROS generation and increased ATP production. These cardioprotective effects were abolished by PINK1(a crucial mitophagy protein) knockdown or the autophagy inhibitor 3-Methyladenine. The protective effect of AA was also inhibited by indomethacin and Cay10441, a prostacyclin receptor antagonist. Furthermore, diabetic Sprague Dawley rats were subjected to coronary ligation for 40 min and AA treatment (10 mg/day per animal gavaged) decreased myo...