Circulating Mitochondrial Open Reading Frame of the 12S Ribosomal RNA Type-c Is Higher in Acute Coronary Syndrome and Is a Prognostic Biomarker for Major Cardiac Events in Patients With Acute Myocardial Infarction: A Case-Control Study.

BACKGROUND: To date, the role of MOTS-c (mitochondrial open reading frame of the 12S ribosomal RNA type-c) in acute coronary syndrome remains largely unknown. We measured circulating MOTS-c levels, markers of oxidative stress, and blood biochemical parameters in patients with acute coronary syndrome and examined their relationship with major adverse cardiac events (MACE). METHODS: A total of 400 subjects were recruited and divided into 3 groups: normal controls, unstable angina, and acute myocardial infarction, based on the clinical data and angiography results. Serum MOTS-c and thiobarbituric acid reactive substances were measured upon initial admission. Hospitalization data, major adverse cardiac events, and a follow-up duration of 18 months were recorded. RESULTS: The serum levels of MOTS-c and thiobarbituric acid reactive substances were higher in patients with acute coronary syndrome and there was a positive correlation between MOTS-c and thiobarbituric acid reactive substances. In addition, MOTS-c levels showed a high sensitivity of 0.890 (cutoff value, 326.65 [95% CI, 253.41-631.84]; area under the curve, 0.739 [95% CI, 0.647-0.832],<0.001) in predicting the occurrence of unstable angina and acute myocardial infarction in the general population. Our data also showed that MOTS-c/thiobarbituric acid reactive substances levels could be used to predict major adverse cardiac events in the group with acute myocardial infarction, with a sensitivity of 0.800 and specificity of 0.667 (cutoff value, 48.26 ng/umol [95% CI, 45.43-90.16 ng/umol]; area under the curve, 0.718 [95% CI, 0.598-0.839],=0.003). In vitro studies demonstrated that oxidative stress induces MOTS-c levels and MOTS-c treatment reduces hypoxia-induced oxidative stress through activating antioxidants. CONCLUSIONS: The circulating MOTS-c is associated with an increased risk of acute coronary syndrome and the imbalance between oxidative stress and circulating MOTS-c may play a role in predicting major adverse cardiac events in patients with acute myocardial infarction.