A b s t r a c tBackground: Coronary artery occlusion does not always manifest with ST-elevation, and some patients can have patent coronary vessel. Aim:We evaluated circulating microRNA (miRNA) profiles to discriminate subjects with infarct-related artery (IRA) occlusion. Methods and results:Patients (n = 43) with uncomplicated acute coronary syndrome and positive troponins were classified with respect to patent vs. occluded IRA or ST-elevation vs. non-ST elevation MI (STEMI vs. NSTEMI). Expression levels of serum miRNAs (miR-1, -16, -34a, -122, -124, -208b, -133a/b, -375, and -499) were analysed. Out of 16 STEMI and 27 NSTEMI patients, IRA occlusion was noted in 12 and 15 patients, respectively. The remaining four STEMI and 12 NSTEMI patients had patent IRA. STEMI patients had higher troponin T levels and a 3.83-fold higher miR-134 expression (p < 0.025). Patients with the occluded vs. patent IRA had higher levels of miR-133a (fold change: 7.00), miR-133b (4.57), miR-34a (5.50), miR-124 (2.55), and miR-134 (3.45) but no difference in troponin T levels. Receiver operator characteristic analysis identified decision-making miRNAs in occluded vessels: miR-124 (AUC: 0.787, p < 0.001), miR-133b (AUC: 0.704, p = 0.006), and miR-134 (AUC: 0.686, p = 0.016). With respect to STEMI, only miR-134 showed a discriminating value (AUC: 0.725, p = 0.002). Conclusions:The degree of IRA occlusion determines circulating miRNA expression, and specific miRNAs may be useful in indicating patients requiring urgent coronary revascularisation.

IntroductionCirculating microRNAs (miRNAs) levels are potentially important biomarkers and therapeutic targets of cerebral ischemic event (CIE) in patients with internal carotid artery stenosis (ICAS).AimThis prospective study investigated associations between circulating miRNAs and symptomatic and asymptomatic ICAS, carotid plaque morphology and future cardiovascular events.Material and methodsCirculating miRNAs (miR-1-3p, miR-16-5p, miR-34a-5p, miR-124-3p, miR-133a-3p, miR-133b, miR-134-5p, miR-208b-3p, miR-375 and miR-499-5p) were analyzed in 92 consecutive patients with significant ICAS referred for revascularization. Group I comprised 65 subjects (41 males, age 69.3 ±9.7 years) with a recent CIE. Group II comprised 27 patients (15 males, age 68.2 ±8.4 years) with asymptomatic ICAS. The ICAS degree and plaque morphology was assessed by ultrasonography. The incidences of cardiovascular death (CVD), myocardial infarction (MI) and recurrent CIE (CVD/MI/CIE) were recorded prospectively (mean: 38.7 ±3.8 months).ResultsGroups II and I differed significantly in levels of miR-124-3p (p = 0.036), miR-133a-3p (p = 0.043) and miR-134-5p (p = 0.02). Hypoechogenic, as compared to echogenic, plaques differed in levels of miR-124-3p (p = 0.038), miR-34a-5p (p = 0.006), miR-133b (p = 0.048), miR-134-5p (p = 0.045), and miR-375 (p = 0.016), while calcified plaques differed in miR-16-5p (p = 0.023). Ulcerated plaques showed higher levels of miR-1-3p (p = 0.04) and miR-16-5p (p = 0.003), while thrombotic plaques showed lower levels of miR-1-3p (p = 0.032). CVD/MI/CIE occurred in 14 (15.5%) out of 90 follow-up patients. Multivariate Cox and ROC analysis showed associations between miR-1-3p and CVD (AUC = 0.634; HR = 4.84; 95% CI: 1.62–14.5; p = 0.005), MI (AUC = 0.743; HR = 7.8; 95% CI: 2.01–30.0; p = 0.003), and CVD/MI/CIE (AUC = 0.560; HR = 4.6; 95% CI: 1.61–13.1; p = 0.004), while miR-133b was associated with recurrent CIE (AUC = 0.581; HR = 2.25; 95% CI: 1.01–5.02; p = 0.047).ConclusionsA significant difference in levels of selected miRNAs is observed in symptomatic vs. asymptomatic ICAS. Plaque morphology and structure is associated with change of miRNA levels. The expression of miR-1-3p may be a potential prognostic factor for future cardiovascular events.

and intima-media thickness in carotid (CIMT) or femoral arteries. 2 CIMT, reflecting vascular age, is independently associated with the extent of atherosclerosis and ischemic cardiovascular events. 3-9 According to current guidelines, in patients with symptomatic atherosclerotic lesions and risk factors, INTRODUCTION Atherosclerotic progression is the main factor responsible for ischemic cardiovascular events, such as major adverse cerebral and coronary events (MACCEs), as well as chronic ischemia. 1 There is evidence for a relationship between atherosclerotic development and peripheral artery stiffness, and endothelial dysfunction

This study shows that although most investigated miRs levels differ significantly between patients with ACS and CIE, similar levels of circulating miR-1-3p, miR-133a-3p, miR-133b, and miR-375 were observed; furthermore, we identified several common miRs as possible risk factors for recurrent cardiovascular events.