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Anatol J Cardiol. 2019 Apr;21(5):261-271. doi: 10.14744/AnatolJCardiol.2019.11456.

Treatment with metformin prevents myocardial ischemia-reperfusion injury via STEAP4 signaling pathway.

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Department of Cardiology, The First Hospital of China Medical University; Shenyang-China.



This study aims to investigate the underlying mechanism of metformin in reducing myocardial apoptosis and improving mitochondrial function in rats and H9c2 cells subjected with myocardial ischemia-reperfusion injury (I/R).


Following pretreatment with metformin, male Sprague-Dawley (SD) rats were used to establish an ischemia-reperfusion (I/R) model in vivo. Serum creatinine kinase-MB (CK-MB) and cardiac troponin T (cTnT) levels were examined by ELISA. Infarct size and apoptosis were measured by TTC staining and TUNEL assay. Pathological changes were evaluated by HE staining. H9c2 cells were used to establish a hypoxia-reoxygenation (H/R) model in vitro. Cell apoptosis and mitochondrial membrane potential (MMP) were examined by flow cytometry and Rhodamine 123. The expression levels of STEAP4, Bcl-2, Bax and GAPDH in both myocardial tissues and H9c2 cells were determined by western blotting.


We found that metformin decreased infarct size, increased expression of STEAP4, mitigated myocardial apoptosis and increased mitochondrial membrane potential (MMP) when the models were subjected to H/R or I/R injuries. However, STEAP4 knockdown significantly abrogated the beneficial effect of metformin.


We further demonstrated the protective effect of metformin on cardiomyocytes, which might be at least partly attributable to upregulation of STEAP4. Therefore, STEAP4 might be a new target to decrease apoptosis and rescue mitochondrial function in myocardial ischemia-reperfusion injury.

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