Division of Cardiology, Department of Internal Medicine, Chungnam National University Hospital, Chungnam National University School of Medicine, 282 Munhwa-ro, Jung-gu, Daejeon 35015, Korea.
Department of Biomedical Science, Jungwon University, Goesan-gun 28024, Korea.
Int J Mol Sci. 2017 Dec 8;18(12):2664. doi: 10.3390/ijms18122664.
Myocarditis is an inflammatory disease of the myocardium that causes cardiogenic shock and death. However, endomyocardial biopsy that is, the gold standard for a diagnosis is limited. Apurinic/apyrimidinic endonuclease 1/redox effector factor-1 (APE1/Ref-1) is a multifunctional protein, which is involved in DNA-based excision repair pathway, and in redox signaling, its changes are observed in various cardiovascular diseases including hypertension and coronary artery disease. We analyzed serum APE1/Ref-1 in experimental murine myocarditis. To induce myocarditis, coxsackievirus B3 was injected intraperitoneally to BALB/c mice. The serum APE1/Ref-1, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin I were measured. The histology and virus titers measurements were performed. The troponin I and inflammation were significantly elevated at day 3, peaked to day 7 and decreased at day 10. The NT-proBNP and virus titers were significantly peaked at day 3, and dropped at day 7 and 10. The serum APE1/Ref-1 was gradually raised and its elevation is still maintained until a later time, namely day 10. Also, its level was positively correlated with myocardial inflammation, reflecting severity of myocardial injury. We suggest that serum APE1/Ref-1 can be used to assess for myocardial injury in viral myocarditis without endomyocardial biopsy.
心肌炎是一种心肌炎症性疾病,可导致心源性休克和死亡。然而,作为诊断的金标准——心内膜心肌活检的应用受到限制。脱嘌呤/脱嘧啶核酸内切酶 1/氧化还原效应因子-1(APE1/Ref-1)是一种多功能蛋白,参与 DNA 碱基切除修复途径和氧化还原信号转导,其变化在高血压和冠状动脉疾病等多种心血管疾病中都有观察到。我们分析了实验性鼠心肌炎患者的血清 APE1/Ref-1。为诱导心肌炎,我们将柯萨奇病毒 B3 腹腔注射到 BALB/c 小鼠体内。检测血清 APE1/Ref-1、N 末端脑钠肽前体(NT-proBNP)和肌钙蛋白 I 的水平,进行组织学和病毒滴度检测。肌钙蛋白 I 和炎症在第 3 天显著升高,第 7 天达到峰值,第 10 天下降。NT-proBNP 和病毒滴度在第 3 天显著升高,第 7 天和第 10 天下降。血清 APE1/Ref-1 逐渐升高,其升高水平一直持续到第 10 天。此外,其水平与心肌炎症呈正相关,反映了心肌损伤的严重程度。我们认为,血清 APE1/Ref-1 可用于评估病毒性心肌炎而无需进行心内膜心肌活检的心肌损伤。