Universität zu Köln

Hortmann, Marcus, Robinson, Samuel, Mohr, Moritz, Mauler, Maximillian, Stallmann, Daniela, Reinoehl, Jochen, Duerschmied, Daniel, Peter, Karlheinz, Carr, James, Gibson, C. Michael, Bode, Christoph and Ahrens, Ingo (2019). The mitochondria-targeting peptide elamipretide diminishes circulating HtrA2 in ST-segment elevation myocardial infarction. Eur. Heart J.-Acute Cardiovasc. Care, 8 (8). S. 695 - 703. LONDON: SAGE PUBLICATIONS LTD. ISSN 2048-8734

Full text not available from this repository.

Abstract

Background: The extent of myocardial damage in patients with ST-segment elevation myocardial infarction (STEMI) depends on both the time to reperfusion as well as injury induced by ischaemia-reperfusion resulting in a cascade of cellular and humoral reactions. As a consequence of ischaemia-reperfusion in the heart, the high-temperature requirement serine peptidase 2 (HtrA2) is translocated from the mitochondria to the cytosol, whereupon it induces protease activity-dependent apoptosis mediated via caspases. Myocardial damage induced by reperfusion cannot be monitored due to a current lack in specific biomarkers. We examined the serum level of HtrA2 as a potentially novel biomarker for mitochondrial-induced cardiomyocyte apoptosis. Methods: After informed consent, peripheral blood was obtained from patients (n=19) with first-time acute anterior STEMI after percutaneous coronary intervention. Within this group, 10 of the patients received the mitochondria-targeting peptide elamipretide (phase 2a clinical study EMBRACE (NCT01572909)). Blood was also obtained from a control group of healthy donors (n=16). The serum level of HtrA2 was measured by an enzyme-linked immunosorbent assay (ELISA). In a murine model of myocardial ischaemia-reperfusion injury, HtrA2 was determined in plasma by ELISA after left anterior descending artery occlusion. Results: HtrA2 median was significantly increased in patients with STEMI compared to healthy controls 392.4 (240.7-502.8) pg/mL vs. 1805.5 (981.3-2220.1) pg/mL (P <= 0.05). Elamipretide significantly reduced the HtrA2 median serum level after myocardial infarction 1805.5 (981.3-2220.1) pg/mL vs. 496.5 (379.4-703.8) pg/mL (P <= 0.05). Left anterior descending artery occlusion in mice significantly increased HtrA2 mean in plasma (117.4 fg/ml +/- SEM 28.1 vs. 525.2 fg/ml +/- SEM 96; P <= 0.05). Conclusion: Compared to healthy controls, we found significantly increased serum levels of HtrA2 in patients with STEMI. The result was validated in a murine model of myocardial ischaemia-reperfusion injury. In humans the increased serum level was significantly reduced by the mitochondria-targeting peptide elamipretide. In conclusion, HtrA2 is detectable in serum of patients with STEMI and might present a novel biomarker for mitochondrial-induced cardiomyocyte apoptosis. Consequently, HtrA2 may also show promise as a biomarker for the identification of ischaemia-reperfusion injury. However, this must be validated in a lager clinical trial.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hortmann, Marcus UNSPECIFIED UNSPECIFIED UNSPECIFIED Robinson, Samuel UNSPECIFIED UNSPECIFIED UNSPECIFIED Mohr, Moritz UNSPECIFIED UNSPECIFIED UNSPECIFIED Mauler, Maximillian UNSPECIFIED UNSPECIFIED UNSPECIFIED Stallmann, Daniela UNSPECIFIED UNSPECIFIED UNSPECIFIED Reinoehl, Jochen UNSPECIFIED UNSPECIFIED UNSPECIFIED Duerschmied, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Peter, Karlheinz UNSPECIFIED UNSPECIFIED UNSPECIFIED Carr, James UNSPECIFIED UNSPECIFIED UNSPECIFIED Gibson, C. Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Bode, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Ahrens, Ingo UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-126011
DOI:	10.1177/2048872617710789
Journal or Publication Title:	Eur. Heart J.-Acute Cardiovasc. Care
Volume:	8
Number:	8
Page Range:	S. 695 - 703
Date:	2019
Publisher:	SAGE PUBLICATIONS LTD
Place of Publication:	LONDON
ISSN:	2048-8734
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language REPERFUSION INJURY; CYTOCHROME-C; CELL-DEATH; OMI/HTRA2; APOPTOSIS; ISCHEMIA; RELEASE Multiple languages Cardiac & Cardiovascular Systems Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12601