In:
European Heart Journal: Acute Cardiovascular Care, Oxford University Press (OUP), Vol. 8, No. 8 ( 2019-12), p. 695-702
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
2048-8726
,
2048-8734
DOI:
10.1177/2048872617710789
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2019
detail.hit.zdb_id:
2663340-1
