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Treatment with metformin prevents myocardial ischemia-reperfusion injury via STEAP4 signaling pathway [Anatol J Cardiol]
Anatol J Cardiol. 2019; 21(5): 261-271 | DOI: 10.14744/AnatolJCardiol.2019.11456  

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

Ting Luo, Xianli Zeng, Wenqi Yang, Yuelan Zhang
Department of Cardiology, The First Hospital of China Medical University; Shenyang-China

Objectives: 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).
Method: 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.
Results: 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.
Conclusions: 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.

Keywords: metformin, myocardial ischemia–reperfusion injury, apoptosis, STEAP4


Ting Luo, Xianli Zeng, Wenqi Yang, Yuelan Zhang. Treatment with metformin prevents myocardial ischemia-reperfusion injury via STEAP4 signaling pathway. Anatol J Cardiol. 2019; 21(5): 261-271

Corresponding Author: Yuelan Zhang, China


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