{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T07:57:03Z","timestamp":1762761423572},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2017,5,23]],"date-time":"2017-05-23T00:00:00Z","timestamp":1495497600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["European Heart Journal: Acute Cardiovascular Care"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:sec><jats:title>Background:<\/jats:title><jats:p> 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\u2013reperfusion resulting in a cascade of cellular and humoral reactions. As a consequence of ischaemia\u2013reperfusion 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. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p> 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\u2013reperfusion injury, HtrA2 was determined in plasma by ELISA after left anterior descending artery occlusion. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p> HtrA2 median was significantly increased in patients with STEMI compared to healthy controls 392.4 (240.7\u2013502.8) pg\/mL vs. 1805.5 (981.3\u20132220.1) pg\/mL ( P\u2a7d0.05). Elamipretide significantly reduced the HtrA2 median serum level after myocardial infarction 1805.5 (981.3\u20132220.1) pg\/mL vs. 496.5 (379.4\u2013703.8) pg\/mL ( P\u2a7d0.05). Left anterior descending artery occlusion in mice significantly increased HtrA2 mean in plasma (117.4 fg\/ml\u00b1SEM 28.1 vs. 525.2 fg\/ml\u00b1SEM 96; P\u2a7d0.05). <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion:<\/jats:title><jats:p> 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\u2013reperfusion 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\u2013reperfusion injury. However, this must be validated in a lager clinical trial. <\/jats:p><\/jats:sec>","DOI":"10.1177\/2048872617710789","type":"journal-article","created":{"date-parts":[[2017,5,23]],"date-time":"2017-05-23T15:00:56Z","timestamp":1495551656000},"page":"695-702","update-policy":"http:\/\/dx.doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":15,"title":["The mitochondria-targeting peptide elamipretide diminishes circulating HtrA2 in ST-segment elevation myocardial infarction"],"prefix":"10.1093","volume":"8","author":[{"given":"Marcus","family":"Hortmann","sequence":"first","affiliation":[{"name":"Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Germany"},{"name":"Department of Medicine, Monash University, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moritz","family":"Mohr","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maximillian","family":"Mauler","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Stallmann","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jochen","family":"Rein\u00f6hl","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Duerschmied","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karlheinz","family":"Peter","sequence":"additional","affiliation":[{"name":"Department of Medicine, Monash University, Australia"},{"name":"Baker IDI Heart and Diabetes Institute, Melbourne, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Carr","sequence":"additional","affiliation":[{"name":"Stealth BioTherapeutics Inc., Newton, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C Michael","family":"Gibson","sequence":"additional","affiliation":[{"name":"PERFUSE Study Group, Harvard Medical School, Boston, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Bode","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingo","family":"Ahrens","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Germany"},{"name":"Augustinerinnen Hospital, Cologne, Academic Teaching Hospital University of Cologne, 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