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], P <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], P =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.