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

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.

journal_name

DNA Cell Biol

journal_title

DNA and cell biology

authors

Li W,Li W,Leng Y,Xiong Y,Xia Z

doi

10.1089/dna.2019.5097

subject

Has Abstract

pub_date

2020-02-01 00:00:00

pages

210-225

issue

2

eissn

1044-5498

issn

1557-7430

journal_volume

39

pub_type

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