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Prospective Study on Circulating MicroRNAs and Risk of Myocardial Infarction
Study Questions:
Are circulating levels of microRNAs (miRNAs) predictive of myocardial infarction (MI)?
Methods:
Nineteen candidate miRNAs were quantified by real-time polymerase chain reaction (RT-PCR) in 820 participants.
Results:
Three miRNAs were consistently related to incident MI: miR-126 showed a positive association (hazard ratio [HR], 2.69; p = 0.002), whereas miR-223 and miR-197 were inversely associated with disease risk (HR, 0.47; p = 0.002, and 0.56, p = 0.036). To determine their cellular origin, healthy volunteers underwent limb ischemia-reperfusion (IR) generated by thigh cuff inflation, and plasma miRNA changes were analyzed at baseline, 10 minutes, 1 hour, 5 hours, 2 days, and 7 days. Computational analysis identified six distinct miRNA clusters, one of which included all miRNAs associated with the risk of future MI. It was characterized by early (1 hour) and sustained activation (7 days) post–IR injury and consisted of miRNAs predominantly expressed in platelets.
Conclusions:
In subjects with subsequent MI, differential coexpression patterns of circulating miRNAs occur around endothelium-enriched miR-126, with platelets being a major contributor to this miRNA signature.
Perspective:
miRNAs are short RNA molecules that regulate the expression of other genes. More than 1,000 miRNAs have been identified, and most of the genome may be influenced by these molecules. miRNAs appear to play important roles in many complex disease processes such as atherothrombosis, and could represent therapeutic targets. Although causality is not proven, this study demonstrates in a prospective fashion that specific miRNAs present in the circulation may be predictive of vascular events and could serve as useful biomarkers, especially as we learn more about the pathways they regulate.
Keywords: Risk, Mutagenesis, Myocardial Infarction, Reperfusion Injury, Thigh, RNA, Viral, Gene Expression Profiling, Cardiovascular Diseases, MicroRNAs, Blood Platelets, Oligonucleotide Array Sequence Analysis
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