Research Paper Volume 16, Issue 1 pp 617—626
GDF15 restrains myocardial ischemia-reperfusion injury through inhibiting GPX4 mediated ferroptosis
- 1 Department of Cardiovascular Medicine, The 900 Hospital of the Joint Service Support Force of the People’s Liberation Army of China, Fuzhou 350001, Fujian, China
Received: August 15, 2023 Accepted: November 28, 2023 Published: January 10, 2024
https://doi.org/10.18632/aging.205402How to Cite
Copyright: © 2024 Gao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Growth and differentiation factor 15 (GDF15) has been proved to regulate the process of Myocardial ischemia-reperfusion injury (MIRI), which is a serious complication of reperfusion therapy. The present study aimed to explore if GDF15 could regulate the MIRI-induced ferroptosis.
Method: MIRI animal model was established by ligating the left anterior descending coronary artery. Oxygen-glucose deprivation/reoxygenation (OGD/R) cell model was established to imitate MIRI in vitro. The indicators of ferroptosis including mitochondrial damage, GPX4, FACL4, XCT4, and oxidative stress markers were evaluated.
Results: Overexpression of GDF15 greatly inhibited MIRI, improved cardiac function, alleviated MIRI-induced ferroptosis. pc-DNA-GDF15 significantly inhibited the oxidative stress condition and inflammation response. The OGD/R-induced ferroptosis was also inhibited by pc-DNA-GDF15.
Conclusion: We proved that the MIRI-induced ferroptosis could by inhibited by pc-DNA-GDF15 through evaluating mitochondrial damage, MDA, GSH, and GSSG. Our research provides a new insight for the prevention and treatment of MIRI, and a new understanding for the mechanism of MIRI-induced ferroptosis.
Abbreviations
GDF15: Growth and differentiation factor 15; MIRI: Myocardial ischemia-reperfusion injury; OGD/R: Oxygen-glucose deprivation/reoxygenation; AMI: Acute myocardial infarction; CABG: Coronary artery bypass grafting; PCI: Percutaneous coronary intervention; RIPC: Remote ischemic preconditioning; MDA: Malondialdehyde; GSH: Glutathione; GSSG: Oxidized glutathione; HE: Hematoxylin-eosin; LVFS: Left ventricular fractional shortening; LVEF: Left ventricular ejection fraction; IHC: Immunohistochemistry; PBS: Phosphate-buffered saline; PVDF: Polyvinylidene fluoride; FBS: Fetal bovine serum; ANOVA: One-way analysis of variance; GPX4: Glutathione peroxidase 4.