2. Academic Validation
  3. Resveratrol protects cardiomyocytes against ischemia/reperfusion-induced ferroptosis via inhibition of the VDAC1/GPX4 pathway

Resveratrol protects cardiomyocytes against ischemia/reperfusion-induced ferroptosis via inhibition of the VDAC1/GPX4 pathway

  • Eur J Pharmacol. 2024 May 15:971:176524. doi: 10.1016/j.ejphar.2024.176524.
Tie Hu 1,  Hua-Xi Zou 2,  Ze-Yu Zhang 3,  Yi-Cheng Wang 4,  Fa-Jia Hu 1,  Wen-Xiong Huang 4,  Ji-Chun Liu 2,  Song-Qing Lai 5,  Huang Huang 6
Affiliations

Affiliations

  • 1 Department of Cardiovascular Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi, China; Department of Cardiovascular Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi, China.
  • 2 Department of Cardiovascular Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi, China.
  • 3 Institute of Nanchang University Trauma Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330000, Nanchang, China.
  • 4 Department of Cardiovascular Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi, China.
  • 5 Department of Cardiovascular Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi, China. Electronic address: ndyfy03743@ncu.edu.cn.
  • 6 Department of Cardiovascular Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi, China. Electronic address: ndyfy04759@ncu.edu.cn.
PMID: 38561102 DOI: 10.1016/j.ejphar.2024.176524
Abstract

The present study aimed to explore how resveratrol (Res) confers myocardial protection by attenuating Ferroptosis. In vivo and in vitro myocardial ischemia/reperfusion injury (MIRI) models were established, with or without Res pretreatment. The results showed that Res pretreatment effectively attenuated MIRI, as evidenced by increased cell viability, reduced Lactate Dehydrogenase activity, decreased infarct size, and maintained cardiac function. Moreover, Res pretreatment inhibited MIRI-induced Ferroptosis, as shown by improved mitochondrial integrity, increased glutathione level, decreased prostaglandin-endoperoxide synthase 2 level, inhibited iron overload, and abnormal lipid peroxidation. Of note, Res pretreatment decreased or increased voltage-dependent anion channel 1/Glutathione Peroxidase 4 (VDAC1/GPX4) expression, which was increased or decreased via anoxia/reoxygenation (A/R) treatment, respectively. However, the overexpression of VDAC1 via pAd/VDAC1 and knockdown of GPX4 through Si-GPX4 reversed the protective effect of Res in A/R-induced H9c2 cells, whereas the inhibition of GPX4 with RSL3 abolished the protective effect of Res on mice treated with ischemia/reperfusion.Interestingly, knockdown of VDAC1 by Si-VDAC1 promoted the protective effect of Res on A/R-induced H9c2 cells and the regulation of GPX4. Finally, the direct interaction between VDAC1 and GPX4 was determined using co-immunoprecipitation. In conclusion, Res pretreatment could protect the myocardium against MIRI-induced Ferroptosis via the VDAC1/GPX4 signaling pathway.

Keywords

Ferroptosis; GPX4; Ischemia/reperfusion injury; Resveratrol; VDAC1.

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