Introduction
Acute coronary syndrome is characterized by the active, inflamed and unstable atherosclerotic plaque that is vulnerable to rupture, predisposing to lumen occlusion and varying extents of myocardial injury. Plasma microRNA have been examined in the hope of identifying an easily accessible biomarker for acute coronary syndrome. But so far studies have taken a candidate approach and screened only for miRNA that are potentially released from the injured myocardium. Even so, data from these studies are inconsistent and a consensus is yet to be reached.
Aim
We set out to screen for circulating plasma microRNAs to serve as biomarkers for patients with Acute Coronary Syndrome.
Methods and results
We selected patients who suffered from 2 ends of the severity spectrum of acute coronary syndrome vs age-matched healthy controls. These were 20 μsevere” (STEMI: troponin-positive with subsequent rapid deterioration in left ventricular function or death within 5 years), 20 μmild” (unstable angina: troponin-negative with sustained normal left ventricular function and survival at 5 years), and 20 normal healthy volunteers. Blood samples were obtained from patients within 2 weeks of the acute event. We took a non-constrained approach and screened using an array panel consisting of 379 miRNA. We found 32 miRNA that were significantly upregulated (29/32) or downregulated (3/32) in the comparison between patient vs. control (sum of t-statistic>2). We have made a preliminary analysis of these in relation to a full panel of other classical biomarkers and patient clinical details. We selected 4 candidate microRNAs (miR-27b, -103, -323-3p, -652) and proceeded to test the plasma levels of these in a validation cohort of 100 troponin-positive, 100 troponin-negative patients and 100 normal healthy volunteers. miR 27b, -323-3p, -652 were significantly upregulated in disease and hence robustly validated.
Conclusion
miR 27b, -323-3p, -652 strongly associates with the event of acute coronary syndrome. Further work will be required to determine the origin and physiological function of these candidate miRNA, and whether their plasma levels can be used for prognostication purposes.
The Impact of Chronic Repetitive Leg Ischemia on Left Ventricular Function and Severity of Coronary Atherosclerosis in Patients with Acute Coronary Syndrome
