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Cardiovascular Diabetology
Published in: Cardiovascular Diabetology 1/2024

Open Access 01-12-2024 | Myocardial Infarction | Research

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

Authors: Yunhui Lv, Kai Li, Shuo 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, Min Zhang, Chen Shen, Xin Wang, Miao Wang, Zhen Ye, Yongchun Cui

Published in: Cardiovascular Diabetology | Issue 1/2024

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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 |log2 (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, PGI2 and 6-keto-PGF1α, 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 myocardial infarct size, cell apoptosis index, inflammatory cytokines and improved heart function. Scanning electron microscopy showed more intact mitochondria in the border zone of infarcted myocardium in AA treated rats. Lastly, diabetic patients after myocardial infarction had lower plasma levels of AA and 6-keto-PGF1α and reduced cardiac ejection fraction, compared with non-diabetic patients after myocardial infarction. Plasma AA level was inversely correlated with fasting blood glucose.

Conclusions

AA protects against diabetic ischemic myocardial damage by promoting mitochondrial autophagy and renewal, which is related to AA derived PGI2 signaling. AA may represent a new strategy to treat diabetic myocardial ischemic injury.
Appendix
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Metadata
Title
Protective role of arachidonic acid against diabetic myocardial ischemic injury: a translational study of pigs, rats, and humans
Authors
Yunhui Lv
Kai Li
Shuo 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
Min Zhang
Chen Shen
Xin Wang
Miao Wang
Zhen Ye
Yongchun Cui
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2024
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-024-02123-3

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WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

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