Metformin protects cardiomyocytes against oxygen-glucose deprivation injury by promoting autophagic flux through AMPK pathway

Abstract

Metformin has been shown to protect myocardial ischaemia/reperfusion or hypoxia/reoxygenation injury. In our current study, we investigated the effects of metformin on autophagy and its possible underlying mechanisms in in vivo myocardial infarction (MI) model and in vitro oxygen-glucose deprivation (OGD) model. A rat model of MI was made by ligating coronary artery in vivo study. Metformin (200 mg/kg/day) could improve cardiac function, prevent rats from MI-induced injury by reducing myocardial infarct size and apoptosis. Moreover, metformin furtherly promoted autophagy by increasing the protein expression of LC3-II, ATG5, ATG7 and Beclin1, and by involving AMPK pathway during MI. H9c2 cells were treated with metformin (4 mM) in vitro study to assess its effects after exposure to OGD. Metformin increased cell viability and inhibited OGD-induced LDH synthesis and cell apoptosis. Furthermore, metformin increased autophagosome formations as well as expression of autophagy-related proteins, promoted autophagic flux. In addition, metformin augmented the protein level of Bcl-2 and diminished the protein levels of Bax and cleaved caspase-3. Metformin also upregulated p-AMPK expression. Nevertheless, the above-mentioned effects of metformin on H9c2 cells were remarkably eliminated by compound C (an AMPK inhibitor). In summary, we displayed that metformin protected cardiomyocytes against OGD-induced injury and apoptosis by promoting autophagic flux through the AMPK pathway.

Keywords:

• Metformin
• autophagy
• oxygen-glucose deprivation
• myocardial infarction
• H9c2 cell

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was financially supported by the Medical Science and Technology Project of Henan Province [SB201901009], the Joint Co-construction Project of Henan Medical Science and Technology Research Plan, and the Key Research & Development and Promotion of Special Project (Scientific Problem Tackling) of Henan Province [202102310122].