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  2. Ferroptosis Is Involved in Diabetes Myocardial Ischemia/Reperfusion Injury Through Endoplasmic Reticulum Stress

Ferroptosis Is Involved in Diabetes Myocardial Ischemia/Reperfusion Injury Through Endoplasmic Reticulum Stress

  • DNA Cell Biol. 2020 Feb;39(2):210-225. doi: 10.1089/dna.2019.5097.
Wenyuan Li 1 Wei Li 1 Yan Leng 1 Yonghong Xiong 1 Zhongyuan Xia 1
Affiliations

Affiliation

  • 1 Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, P.R. China.
Abstract

Myocardial ischemic disease affects the prognosis in perioperative patients. Diabetes can aggravate myocardial injury. The purpose of this research is to investigate the effect of Ferroptosis in the process of diabetes mellitus (DM) myocardial ischemia/reperfusion (I/R) injury (IRI). Endoplasmic reticulum stress (ERS) is investigated whether aggravates cardiomyocytes injury. Rat DM+I/R (DIR), cell high glucose (HG), hypoxia reoxygenation (H/R), and high-glucose H/R (HH/R) models were established. Ferroptosis inhibitor Ferrostatin-1, Ferroptosis agonist Erastin, ERS inhibitor Salubrinal, and ERS agonist Tunicamycin were administered. Serum creatine kinase-MB (CK-MB), cell viability, Lactate Dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), Reactive Oxygen Species (ROS), and cellular ferrous ion concentration were examined. The level of ACSL4, GPX4, ATF4, CHOP, Bcl-2, and Bax was detected. Myocardial tissue pathological change was detected by hematoxylin-eosin staining. Cardiac function was monitored by invasive hemodynamic measurements. Evans Blue-triphenyltetrazolium chloride double staining was used to detect the myocardial infarct size. In DM+sham (DS) (or HG) and I/R (or H/R) models, cardiomyocytes were injured accompanied by increased level of Ferroptosis and ERS. Moreover, the cell injury was more serious in rat DIR or cell HH/R models. Inhibition of Ferroptosis in DIR model could reduce ERS and myocardial injury. Inhibition of Ferroptosis in H9c2 cells HG, H/R, and HH/R models could reduce cell injury. Erastin could aggravate ERS and cell injury by stimulating Ferroptosis in HH/R cell model. Meanwhile, inhibition of ERS could alleviate Ferroptosis and cell injury. Ferroptosis is involved in DIR injury that is related to ERS. Moreover, inhibition of Ferroptosis can alleviate DIR injury, which may provide a therapeutic regent for myocardial ischemic disease.

Keywords

diabetes myocardial; endoplasmic reticulum stress; ferroptosis; ischemia/reperfusion.

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