CCAAT/enhancer binding protein homologous protein knockdown alleviates hypoxia-induced myocardial injury in rat cardiomyocytes exposed to high glucose

Yang,Wenqi; Wu,Fang; Luo,Ting; Zhang,Yuelan

doi:10.3892/etm.2018.5944

CCAAT/enhancer binding protein homologous protein knockdown alleviates hypoxia-induced myocardial injury in rat cardiomyocytes exposed to high glucose

Authors:
- Wenqi Yang
- Fang Wu
- Ting Luo
- Yuelan Zhang
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Affiliations: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: March 9, 2018 https://doi.org/10.3892/etm.2018.5944
Pages: 4213-4222
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Diabetic patients are more sensitive to ischemic injury than non‑diabetics. Endoplasmic reticulum (ER) stress has been reported to be closely associated with the pathophysiology of ischemic injury in diabetes. The aim of the present study was to investigate the mechanisms involved in the progression of diabetes complicated by myocardial infarction (MI) and further verify the role of CCAAT/enhancer binding protein (C/EBP)‑homologous protein (CHOP) using an in vitro model of diabetes/MI. The rats were exposed to 65 mg/kg streptozotocin (STZ) and left anterior descending (LAD) coronary artery ligation. ST‑segment elevation, heart rate, left ventricular systolic pressure (LVSP) and LV end‑diastolic pressure (LVEDP) were measured. Serum creatinine kinase‑MB (CK‑MB) and cardiac troponin T (cTnT) levels were examined by ELISA. Infarct size and apoptosis were measured by triphenyltetrazolium chloride staining and terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling assay. Pathological changes were evaluated by hematoxylin and eosin staining. H9c2 cells were used to establish an in vitro model of diabetes complicated by MI. Following CHOP knockdown, cell viability, cell cycle distribution and apoptosis were examined by Cell Counting Kit‑8 assay, flow cytometry and Hoechst staining. Glucose‑regulated protein 78 (GRP78), CHOP, B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), endoplasmic reticulum oxidoreductase 1 (Ero1)‑α, Ero1β and protein disulfide isomerase (PDI) levels in both myocardial tissues and H9c2 cells were determined by western blotting. In the present study, diabetes complicated by MI promoted ST‑segment elevation and myocardial apoptosis, increased infarct size, induced pathological changes and elevated LVEDP, CK‑MB, cTnT, GRP78, CHOP, Bax, Ero1α, Ero1β and PDI; however, it decreased heart rate, LVSP and Bcl‑2. Additionally, high glucose combined with hypoxic treatment reduced cell viability, induced cell cycle arrest at G1 phase, promoted cell apoptosis, and activated the GRP78/CHOP and Ero1/PDI signaling pathways, which were reversed by CHOP knockdown. Thus, CHOP may be an effective therapeutic target for the treatment of diabetes complicated by MI.

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