Circulating HtrA2 as a novel biomarker for mitochondrial induced cardiomyocyte apoptosis and ischemia-reperfusion injury in ST-segment elevation myocardial infarction. (15th September 2017)

• Record Type: Journal Article
• Authors: Hortmann, M.; Robinson, S.; Mohr, M.; Haenel, D.; Mauler, M.; Stallmann, D.; Reinoehl, J.; Duerschmied, D.; Peter, K.; Bode, C.; Ahrens, I.
• Is Part Of: International journal of cardiology. Volume 243(2017)
• Page Start: 485
• Page End: 491
• Publication Date: 2017-09-15
• Subjects: ST-segment elevation myocardial infarction -- Apoptosis -- Ischemia-reperfusion injury -- Mitochondria -- HtrA2; Cardiology -- Periodicals; Electronic journals; 616.12
• DOI: 10.1016/j.ijcard.2017.05.088
• Languages: English
• ISSNs: 0167-5273

Abstract

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.