A MicroRNA Signature in Acute Coronary Syndrome Patients and Modulation by Colchicine

Abstract

Background: Circulating microRNAs (miRNAs) may play a pathogenic role in acute coronary syndromes (ACS). It is not yet known if miRNAs dysregulated in ACS are modulated by colchicine. We profiled miRNAs in plasma samples simultaneously collected from the aorta, coronary sinus, and right atrium in patients with ACS. Methods: A total of 396 of 754 miRNAs were detected by TaqMan real-time polymerase chain reaction from EDTA-plasma in a discovery cohort of 15 patients (n = 3 controls, n = 6 ACS standard therapy, n = 6 ACS standard therapy plus colchicine). Fifty-one significantly different miRNAs were then measured in a verification cohort of 92 patients (n = 13 controls, n = 40 ACS standard therapy, n = 39 ACS standard therapy plus colchicine). Samples were simultaneously obtained from the coronary sinus, aortic root, and right atrium. Results: Circulating levels of 30 of 51 measured miRNAs were higher in ACS standard therapy patients compared to controls. In patients with ACS, levels of 12 miRNAs (miR-17, -106b-3p, -191, -106a, -146a, -130a, -223, -484, -889, -425-3p, -629, -142-5p) were lower with colchicine treatment. Levels of 7 of these 12 miRNA were higher in ACS standard therapy patients compared to controls and returned to levels seen in control individuals after colchicine treatment. Three miRNAs suppressed by colchicine (miR-146a, miR-17, miR-130a) were identified as regulators of inflammatory pathways. MicroRNAs were comparable across sampling sites with select differences in the transcoronary gradient of 4 miRNA. Conclusion: The levels of specific miRNAs elevated in ACS returned to levels similar to control individuals following colchicine. These miRNAs may mediate ACS (via inflammatory pathways) or increase post-ACS risk, and could be potentially used as biomarkers of treatment efficacy.

Postpartum circulating microRNA enhances prediction of future type 2 diabetes in women with previous gestational diabetes

“…We profiled 754 known/ validated human miRNAs using OpenArray panels on the discovery set of samples. As expected for plasma samples [38,39], 273 miRNAs were expressed in at least one of the samples (Fig. 1a); with the remaining miRNAs being undetectable (C t value = 39).…”

Nourin-Dependent miR-137 and miR-106b: Novel Early Inflammatory Diagnostic Biomarkers for Unstable Angina Patients

“…Clinically high levels of Nourin were detected in ACS and AMI patients, but not in symptomatic noncardiac patients and healthy subjects [17], suggesting a potential use of the Nourin biomarker to rule out myocardial ischemia for symptomatic patients having noncardiac causes. Recently, aberrant miRNAs have been reported to play a role in the pathogenesis of cardiovascular diseases, and they are involved in vascular dysfunction, apoptosis, autophagy, inflammation, and angiogenesis [9,18,[31][32][33]. In the present study, we applied a bioinformatics analysis to elucidate the underlying molecular mechanism associated with Nourin protein, and accordingly, the topological characteristics between Nourin protein sequence and miRNAs-mediated interactions network associated with myocardial ischemia were retrieved.…”

Colchicine Use in Acute Coronary Syndromes: An Update

“…40 In addition, the follow-up was also short, as 3 studies 40,43,44 reported only 1-month follow-up duration and 1 study 41 reported a 12-month follow-up period. The duration of colchicine treatment is also heterogeneous, varying between 1 day, 36,38,40,42 5 days, 35 1 month, 43,44 and 1 year. 41 The contradictory results regarding the effect of colchicine on hs-CRP levels could be explained by differences in baseline values between studies.…”

“…Colchicine significantly lowered the expression of 12 miRNAs, demonstrating once again its potential role in reducing acute inflammation. 42…”

“…Colchicine significantly lowered the expression of 12 miRNAs, demonstrating once again its potential role in reducing acute inflammation. 42 Alongside these promising results, there were a few studies that did not associate colchicine use with an amelioration of inflammation in patients with AMI.…”