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循环中的HtrA2作为ST段抬高型心肌梗死中线粒体诱导的心肌细胞凋亡和缺血再灌注损伤的新型生物标志物。

Circulating HtrA2 as a novel biomarker for mitochondrial induced cardiomyocyte apoptosis and ischemia-reperfusion injury in ST-segment elevation myocardial infarction.

作者信息

Hortmann M, Robinson S, Mohr M, Haenel D, Mauler M, Stallmann D, Reinoehl J, Duerschmied D, Peter K, Bode C, Ahrens I

机构信息

Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Germany.

Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Germany; Department of Medicine, Monash University, Melbourne, Australia.

出版信息

Int J Cardiol. 2017 Sep 15;243:485-491. doi: 10.1016/j.ijcard.2017.05.088. Epub 2017 May 24.

DOI:10.1016/j.ijcard.2017.05.088

PMID:28602551

Abstract

BACKGROUND

Ischemia-reperfusion (I/R) injury in ST-segment elevation myocardial infarction (STEMI) significantly contributes to overall myocardial damage. As a consequence of I/R injury in the heart, the high-temperature requirement protein A2 (HtrA2) is released from the mitochondrial intermembrane space of cardiomyocytes to the cytoplasm, whereupon it induces apoptosis.

METHODS

Serum was obtained from STEMI (n=37), non-ST-segment elevation myocardial infarction (NSTEMI) (n=20), stable coronary artery disease (CAD) (n=17) and patients with CAD excluded (n=9). In STEMI, I/R injury was assessed via measurement of ST-segment resolution.

RESULTS

HtrA2 was significantly increased in STEMI compared to NSTEMI, stable CAD and patients with CAD excluded (981.3 (IQR: 543.5-1526.2)pg/mL vs. 494.5 (IQR: 413.8-607)pg/mL vs. 291 (IQR: 239-458.5)pg/mL vs. 692.2 (IQR: 276.6-964.7)pg/mL; p≤0.0001). STEMI patients with HtrA2 level of at least the median or above had a higher peak creatine kinase (CK) (p=0.0002) and cardiac troponin T levels (cTnT) (p=0.0019). Significantly more STEMI patients with HtrA2 levels of at least the median or above were identified as I/R injury (87% vs. 42%; p<0.0001). Serum HtrA2 demonstrated a superior area under a curve in a receiver operating characteristic analysis for predicting I/R injury compared to CK, creatine kinase myocardial-band (CK-MB) and cTnT levels (AUC=0.7105 vs. AUC=0.5632 vs. AUC=0.5660 vs. AUC=0.5407 respectively).

CONCLUSION

HtrA2 shows promise as a novel potential biomarker for mitochondrial-induced cardiomyocyte apoptosis and may help to identify I/R injury after STEMI.

摘要

背景

ST段抬高型心肌梗死（STEMI）中的缺血再灌注（I/R）损伤是导致整体心肌损伤的重要因素。作为心脏I/R损伤的结果，高温需求蛋白A2（HtrA2）从心肌细胞的线粒体外膜间隙释放到细胞质中，进而诱导细胞凋亡。

方法

采集STEMI患者（n = 37）、非ST段抬高型心肌梗死（NSTEMI）患者（n = 20）、稳定型冠状动脉疾病（CAD）患者（n = 17）以及排除CAD的患者（n = 9）的血清。在STEMI患者中，通过测量ST段回落情况评估I/R损伤。

结果

与NSTEMI患者、稳定型CAD患者以及排除CAD的患者相比，STEMI患者的HtrA2水平显著升高（分别为981.3（四分位间距：543.5 - 1526.2）pg/mL vs. 494.5（四分位间距：413.8 - 607）pg/mL vs. 291（四分位间距：239 - 458.5）pg/mL vs. 692.2（四分位间距：276.6 - 964.7）pg/mL；p≤0.0001）。HtrA2水平至少处于中位数及以上的STEMI患者肌酸激酶（CK）峰值（p = 0.0002）和心肌肌钙蛋白T（cTnT）水平更高（p = 0.0019）。HtrA2水平至少处于中位数及以上的STEMI患者中，被判定为I/R损伤的比例显著更高（87% vs. 42%；p < 0.0001）。在预测I/R损伤的受试者工作特征分析中，血清HtrA2曲线下面积优于CK、肌酸激酶同工酶（CK-MB）和cTnT水平（曲线下面积分别为0.7105 vs. 0.5632 vs. 0.5660 vs. 0.5407）。