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World Journal of Emergency Medicine ›› 2022, Vol. 13 ›› Issue (2): 106-113.doi: 10.5847/wjem.j.1920-8642.2022.021

• Original Articles • Previous Articles     Next Articles

The expression of oxidative stress genes related to myocardial ischemia reperfusion injury in patients with ST-elevation myocardial infarction

Qian-lin Gu1, Peng Jiang1, Hui-fen Ruan2, Hao Tang1, Yang-bing Liang1, Zhong-fu Ma1, Hong Zhan1()   

  1. 1Emergency Department, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510000, China
    2Huangpu District Emergency Department, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510000, China
  • Received:2020-06-09 Accepted:2020-12-20 Online:2021-11-19 Published:2022-03-01
  • Contact: Hong Zhan E-mail:zhanhong81@126.com

Abstract:

BACKGROUND: We aimed to investigate the gene expression of myocardial ischemia/reperfusion injury (MIRI) in patients with acute ST-elevation myocardial infarction (STEMI) using stress and toxicity pathway gene chip technology and try to determine the underlying mechanism.
METHODS: The mononuclear cells were separated by ficoll centrifugation, and plasma total antioxidant capacity (T-AOC) was determined by the ferric reducing ability of plasma (FRAP) assay. The expression of toxic oxidative stress genes was determined and verified by oligo gene chip and quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, gene ontology (GO) enrichment analysis was performed on DAVID website to analyze the potential mechanism further.
RESULTS: The total numbers of white blood cells (WBC) and neutrophils (N) in the peripheral blood of STEMI patients (the AMI group) were significantly higher than those in the control group (WBC: 11.67±4.85 ×109/L vs. 6.41±0.72 ×109/L, P<0.05; N: 9.27±4.75 ×109/L vs. 3.89±0.81 ×109/L, P<0.05), and WBCs were significantly associated with creatine kinase-myocardial band (CK-MB) on the first day (Y=8.945+0.018X, P<0.05). In addition, the T-AOC was significantly lower in the AMI group comparing to the control group (12.80±1.79 U/mL vs. 20.48±2.55 U/mL, P<0.05). According to the gene analysis, eight up-regulated differentially expressed genes (DEGs) included GADD45A, PRDX2, HSPD1, DNAJB1, DNAJB2, RAD50, TNFSF6, and TRADD. Four down-regulated DEGs contained CCNG1, CAT, CYP1A1, and ATM. TNFSF6 and CYP1A1 were detected by polymerase chain reaction (PCR) to verify the expression at different time points, and the results showed that TNFSF6 was up-regulated and CYP1A1 was down-regulated as the total expression. GO and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis suggested that the oxidative stress genes mediate MIRI via various ways such as unfolded protein response (UPR) and apoptosis.
CONCLUSIONS: WBCs, especially neutrophils, were the critical cells that mediating reperfusion injury. MIRI was regulated by various genes, including oxidative metabolic stress, heat shock, DNA damage and repair, and apoptosis-related genes. The underlying pathway may be associated with UPR and apoptosis, which may be the novel therapeutic target.

Key words: Acute myocardial infarction, Myocardial ischemia/reperfusion injury, Oxidative stress, TNFSF6, CYP1A1, Unfolded protein response