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

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

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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.

Original languageEnglish
Pages (from-to)485-491
Number of pages7
JournalInternational Journal of Cardiology
Volume243
DOIs
Publication statusPublished - 15 Sep 2017

Keywords

  • Apoptosis
  • HtrA2
  • Ischemia-reperfusion injury
  • Mitochondria
  • ST-segment elevation myocardial infarction

Cite this

Hortmann, M. ; Robinson, S. ; Mohr, M. ; Haenel, D. ; Mauler, M. ; Stallmann, D. ; Reinoehl, J. ; Duerschmied, D. ; Peter, K. ; Bode, C. ; Ahrens, I. / Circulating HtrA2 as a novel biomarker for mitochondrial induced cardiomyocyte apoptosis and ischemia-reperfusion injury in ST-segment elevation myocardial infarction. In: International Journal of Cardiology. 2017 ; Vol. 243. pp. 485-491.
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title = "Circulating HtrA2 as a novel biomarker for mitochondrial induced cardiomyocyte apoptosis and ischemia-reperfusion injury in ST-segment elevation myocardial infarction",
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.",
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Circulating HtrA2 as a novel biomarker for mitochondrial induced cardiomyocyte apoptosis and ischemia-reperfusion injury in ST-segment elevation myocardial infarction. / Hortmann, M.; Robinson, S.; Mohr, M.; Haenel, D.; Mauler, M.; Stallmann, D.; Reinoehl, J.; Duerschmied, D.; Peter, K.; Bode, C.; Ahrens, I.

In: International Journal of Cardiology, Vol. 243, 15.09.2017, p. 485-491.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Circulating HtrA2 as a novel biomarker for mitochondrial induced cardiomyocyte apoptosis and ischemia-reperfusion injury in ST-segment elevation myocardial infarction

AU - Hortmann, M.

AU - Robinson, S.

AU - Mohr, M.

AU - Haenel, D.

AU - Mauler, M.

AU - Stallmann, D.

AU - Reinoehl, J.

AU - Duerschmied, D.

AU - Peter, K.

AU - Bode, C.

AU - Ahrens, I.

PY - 2017/9/15

Y1 - 2017/9/15

N2 - 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.

AB - 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.

KW - Apoptosis

KW - HtrA2

KW - Ischemia-reperfusion injury

KW - Mitochondria

KW - ST-segment elevation myocardial infarction

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U2 - 10.1016/j.ijcard.2017.05.088

DO - 10.1016/j.ijcard.2017.05.088

M3 - Article

VL - 243

SP - 485

EP - 491

JO - International Journal of Cardiology

JF - International Journal of Cardiology

SN - 0167-5273

ER -