PIM3 regulates myocardial ischemia/reperfusion injury via ferroptosis

• Published in: Genes & genomics Vol. 46; no. 2; pp. 161 - 170
• Main Authors: Li, Ting, Liu, Fangyao, Tan, Ying, Peng, Yutao, Xu, Xuefeng, Yang, Yushan
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 01.02.2024; Springer Nature B.V
• Subjects: Animal Genetics and Genomics; Animals; Biomedical and Life Sciences; Cardiovascular diseases; Cell survival; Cell viability; Cholecystokinin; Coronary Artery Disease; Cytology; Ferroptosis; Ferroptosis - genetics; Human Genetics; Iron; Ischemia; Life Sciences; Microbial Genetics and Genomics; Myocardial ischemia; Myocardial Reperfusion Injury - genetics; Plant Genetics and Genomics; Rats; Reactive Oxygen Species; Reperfusion; Research Article; Superoxide Dismutase; Ferroptosis; PIM3; Myocardial I/R injury; Cell death; Mechanism
• ISSN: 1976-9571; 2092-9293; 2092-9293
• DOI: 10.1007/s13258-023-01475-6

Background Myocardial ischemia/reperfusion (I/R) injury is closely related with cardiovascular diseases; however, the underlying pathogenic mechanisms remain not fully understood. This study sought to investigate the effect and mechanisms of PIM3 implicated in myocardial I/R injury using a rat model of myocardial I/R injury and a cell model of oxygen–glucose deprivation/reoxygenation (OGD/R) induction. Methods The morphology changes were detected by HE staining while cell viability was accessed by the CCK-8 method. The characteristics of ferroptosis were evaluated by ROS production, MDA content, SOD level, iron content, TfR1, FTH1, and GPX4 expression. Results Myocardial I/R operation increased myocardial tissue damage in rats, while OGD/R treatment reduced the viability of H9c2 cells. Both myocardial I/R operation and OGD/R stimulation increased ferroptosis, as demonstrated by elevated ROS, MDA, iron content, decreased SOD level, upregulation of TfR1, and downregulation of FTH1 and GPX4. Additionally, myocardial I/R modeling or OGD/R treatment enhanced the expression of PIM3. Silencing of PIM3 inhibited ferroptosis, which resulted in alleviated myocardial I/R-induced damage and improved H9c2 cell survival. Conclusions Our findings highlight a vital role of PIM3 in myocardial I/R injury, indicating that PIM3-targeting ferroptosis may be a promising target for the development of novel therapies of myocardial I/R injury-associated diseases.