Nardilysin is a promising biomarker for the early diagnosis of acute coronary syndrome
Nardilysin is a promising biomarker for the early diagnosis of acute coronary syndrome
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DOI：
10.1016/j.ijcard.2017.04.047
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发表时间：
2017-09-15
影响因子：
3.5
通讯作者：
Nishi, Eiichiro
中科院分区：
文献类型：
--
作者：
Chen, Po-Min;Ohnoa, Mikiko;Nishi, Eiichiro
背景：目前还没有用于检测不稳定心绞痛（UA）患者短暂性心肌缺血或早期诊断急性心肌梗死（AMI）的生物标志物。方法和结果：我们对急性冠脉综合征（ACS）发病后不久升高的自身抗体进行了两次连续筛查，并在19种已确定的候选抗原中重点检测金属内肽酶溶血素（NRDC）。回顾性分析93例ACS患者和117例非ACS患者，ACS患者血清NRDC水平明显高于非ACS患者（2073.5 +/- 189.8 pg/ml vs 775.7 +/- 63.4 pg/ml, P < 0.0001）。经受试者工作特征曲线分析，诊断ACS的NRDC曲线下面积为0.822。在连续43例ACS患者（AMI: N = 35, UA: N = 8）的时间过程分析中，即使在UA患者中，AMI和UA患者的血清NRDC水平均在入院时达到峰值，NRDC浓度也明显升高。在AMI小鼠模型中，我们发现冠状动脉结扎后不久，血清NRDC急剧升高，缺血区域NRDC表达降低。在AMI患者的人体尸检样本中，NRDC在梗死区域的表达也有所降低。此外，用H2O2或A23187短时间处理大鼠心肌细胞原代培养可诱导NRDC分泌，且无细胞毒性。结论：NRDC是一种很有前景的早期检测ACS的生物标志物，即使在没有坏死标志物升高的UA患者中也是如此。(C) 2017 Elsevier B.V.版权所有
Background: Biomarkers for detection of transient myocardial ischemia in patients with unstable angina (UA) or for very early diagnosis of acute myocardial infarction (AMI) are not currently available.Methods and results: We performed two sequential screenings of autoantibodies elevated shortly after the onset of acute coronary syndrome (ACS), and focused on metalloendopeptidase nardilysin (NRDC) among 19 identified candidate antigens. In a retrospective analysis among 93 ACS and 117 non-ACS patients, the serum level of NRDC was significantly increased in patients with ACS compared with that in patients with non-ACS (2073.5 +/- 189.8 pg/ml versus 775.7 +/- 63.4 pg/ml, P < 0.0001). The area under the curve of NRDC for the diagnosis of ACS was 0.822 by the receiver operating characteristic curves analysis. In the time course analysis in 43 consecutive ACS patients (AMI: N = 35 and UA: N = 8), serum concentration of NRDC was significantly increased even in UA patients with a peak serum NRDC levels reached at admission both in AMI and UA patients. In a mouse model of AMI, we found an acute increase in serum NRDC and reduced NRDC expression in ischemic regions shortly after coronary artery ligation. NRDC expression was also reduced in infarcted regions in human autopsy samples from AMI patients. Moreover, the short treatment of primary culture of rat cardiomyocytes with H2O2 or A23187 induced NRDC secretion without cell toxicity.Conclusion: NRDC is a promising biomarker for the early detection of ACS, even in UA patients without elevation of necrosis markers. (C) 2017 Elsevier B.V. All rights reserved.