Decision-making microRNAs (miR-124, -133a/b, -34a and -134) in patients with occluded target vessel in acute coronary syndrome

Abstract

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.

Identifying circulating microRNAs as biomarkers of cardiovascular disease: a systematic review

“…Previously described as potential AMI diagnostic markers, miR-133a, miR-208b, 22,35 as well as miR-499 and miR-451, 22 and miR-134 24 levels were reported as higher in STEMI, when compared with non-STEMI. In contrast, two studies of miR-499 24,35 showed no significant difference in miR expression. A combination of miR-486 and miR-150 39 was reported to be sensitive and specific for the discrimination of non-STEMI cases from non-AMI controls, but not for discriminating non-STEMI from STEMI.…”

“…miR-133a, 24,33 miR-134, miR-145, 25 miR-122, and miR-370 26 were associated with CAD presence, even after adjustment for other cardiovascular risk factors. Furthermore, their levels were positively correlated with the severity of CAD quantified by the Gensini score, in other words, may be used to predict both the presence and severity of coronary lesions in CAD patients.…”

“…A single study reported miR-155 40 being associated inversely with complicated pro-atherogenic metabolic risk factors. In separate studies, miR-126, 32 miR-33a/b 26 as well as miR-1, miR-16, miR-122, miR-208b, miR-375, and miR-499 24 were not significantly down-regulated or up-regulated in CAD patients and so not suitable for discriminating CAD patients from patients without CAD.…”

“…Six original studies 24–26,32,33,40 ( Table 1 ) investigated miRs and their value in distinguishing between CAD and non-CAD patients, questioning the need for recurrent diagnostic imaging. …”

“…Five of the studies also investigated the ability to detect differences in levels of miRs between patients with Non-STEMI vs. STEMI 22,24,25,35,39 ( Table 4 ). Previously described as potential AMI diagnostic markers, miR-133a, miR-208b, 22,35 as well as miR-499 and miR-451, 22 and miR-134 24 levels were reported as higher in STEMI, when compared with non-STEMI.…”