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.

Background: Activated platelets release serotonin during acute myocardial infarction (AMI), aggravating myocardial damage and ischemia/reperfusion (I/R) injury. However, serum serotonin and its potential role as a biomarker for myocardial infarction and I/R injury have not been studied so far. Methods: In this investigator-initiated pilot study, we examined 38 patients with ST-segment myocardial infarction (STEMI). We determined serum serotonin levels prior to percutaneous coronary intervention and 8, 16, and 24 h afterwards. We studied whether serum serotonin was associated with I/R injury assessed by ECG analysis and by analysis of TIMI myocardial perfusion grade (TMP) and myocardial blush grade (MGB). Serum serotonin levels were compared to an age-matched control group consisting of patients admitted to the emergency department for any other reason than STEMI. Results: Serum serotonin levels were not elevated in the myocardial infarction group compared to the control cohort and they did not show any timeline kinetics after STEMI. They were not associated with the severity of coronary artery disease, the outcome of coronary angiography, the extent of I/R injury, or the degree of heart failure. Conclusions: Serum serotonin is not suitable as a biomarker after myocardial infarction and in the assessment of I/R injury.