Circulating microRNAs (miRNAs) are emerging as potential biomarkers. We have previously identified a miRNA signature for type 2 diabetes in the general population.Objective
In this study, we sought to explore the association between baseline levels of miRNAs (1995) and incident myocardial infarction (1995-2005) in the Bruneck cohort and determine their cellular origin.Methods and Results
A total of nineteen candidate miRNAs were quantified by real time polymerase chain reactions in 820 participants. In multivariable Cox regression analysis, three miRNAs were consistently and significantly related with incident myocardial infarction: miR-126 showed a positive association (multivariable hazard ratio 2.69 [95%CI 1.45-5.01], P=0.002) while miR-223 and miR-197 were inversely associated with disease risk (multivariable hazard ratio 0.47 [95% CI 0.29-0.75], P=0.002, and 0.56 [95% CI 0.32-0.96], P=0.036). To determine their cellular origin, healthy volunteers were subject to limb ischaemia-reperfusion generated by thigh cuff inflation and plasma miRNA changes were analysed at baseline, at 10 min, 1h, 5h, 2 days and 7 days. Computational analysis using the temporal clustering by affinity propagation algorithm identified six distinct miRNA clusters. One cluster included all miRNAs associated with risk of future myocardial infarction. It was characterized by early (1h) and sustained activation (7 days) post ischaemia-reperfusion injury and consisted of miRNAs predominantly expressed in platelets.Conclusions
In subjects with subsequent myocardial infarction differential co-expression patterns of circulating miRNAs occur around endothelial-enriched miR-126 with platelets being a major contributor to this miRNA signature.