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

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.