RNA modifications in peripheral blood are associated with acute coronary syndrome

Acute coronary syndromes (ACS) trigger inflammatory and immune reactions, yet whether this response is associated with changes in RNA modifications remains poorly understood. We investigated global epitranscriptomic patterns in peripheral blood mononuclear cells (PBMC) from patients with ST-elevation myocardial infarction (STEMI, n = 118), non-ST-elevation myocardial infarction (NSTEMI, n = 22), unstable angina pectoris (UAP, n = 10), and stable angina pectoris (SAP, n = 152). Using liquid chromatography-mass spectrometry, we quantified N1-methyladenosine (m1A), 2'-O-methyladenosine (2'-O-mA), N6-methyladenosine (m6A), N6,2'-O-dimethyladenosine (m6Am), and pseudouridine (Ψ), together with their ratios to unmodified nucleotides. Levels of 2'-O-mA (P = 0.004), m6Am (P < 0.001), and Ψ (P = 0.021) were significantly decreased in STEMI compared with SAP. m6Am was also reduced in UAP (P = 0.037) and NSTEMI (P = 0.012), whereas m1A and m6A did not differ between groups. Among modification ratios, only the m6Am/A ratio declined across ACS subtypes (UAP P = 0.015; NSTEMI P = 0.032; STEMI P = 0.007), indicating relative cap-adjacent hypomethylation. Reduced m6Am correlated inversely with hsCRP (r = -0.19, P < 0.001) and hsTnI (r = -0.24, P < 0.001). In multivariable logistic regression adjusting for age, sex, BMI, and hsCRP, m6Am remained independently associated with STEMI (OR = 0.14, 95% CI 0.02-0.81; P = 0.028). These findings demonstrate selective RNA modification changes in ACS and identify m6Am as an independent epitranscriptomic marker associated with myocardial infarction.