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GDF15 restrains myocardial ischemia-reperfusion injury through inhibiting GPX4 mediated ferroptosis
Qingfeng Gao1, Chao Li1, Peiqi Zhong1
1Department of Cardiovascular Medicine, The 900 Hospital of the Joint Service Support Force of the People’s Liberation Army of China, Fuzhou 350001, Fujian, China.
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.
Insights
Growth and differentiation factor 15 (GDF15) protects against myocardial ischemia-reperfusion injury (MIRI) by inhibiting ferroptosis. This study demonstrates GDF15
Area of Science:
- Cardiovascular Research
- Cellular Biology
- Biochemistry
Background:
- Myocardial ischemia-reperfusion injury (MIRI) is a significant complication of reperfusion therapy.
- Growth and differentiation factor 15 (GDF15) is implicated in regulating MIRI.
- The role of GDF15 in MIRI-induced ferroptosis requires further investigation.
Purpose of the Study:
- To investigate the regulatory role of GDF15 in MIRI-induced ferroptosis.
- To explore the therapeutic potential of GDF15 in mitigating MIRI.
- To elucidate the underlying mechanisms of GDF15's action in MIRI.
Main Methods:
- Established MIRI animal and oxygen-glucose deprivation/reoxygenation (OGD/R) cell models.
- Evaluated ferroptosis indicators: mitochondrial damage, GPX4, FACL4, XCT4.
- Assessed oxidative stress markers, MDA, GSH, and GSSG levels.
Main Results:
- Overexpression of GDF15 significantly inhibited MIRI and alleviated ferroptosis.
- pc-DNA-GDF15 treatment improved cardiac function and reduced oxidative stress and inflammation.
- GDF15 effectively inhibited OGD/R-induced ferroptosis in vitro.
Conclusions:
- GDF15 overexpression inhibits MIRI and associated ferroptosis.
- pc-DNA-GDF15 demonstrates protective effects against MIRI-induced ferroptosis.
- This research offers novel insights into MIRI prevention and treatment strategies.
