Abstract 5019: Circulating MicroRNAs as New Biomarkers of Myocardial Infarction in Man
Background and objective: microRNAs (miRs) are small non-coding RNAs that regulate translation of messenger RNAs (mRNA) into proteins. Recently, it has been suggested that circulating miR may represent a novel class of biomarkers in cancer and liver disease, however no data are available in cardiovascular diseases. Our objective was to examine miR plasma levels in humans and mice with acute myocardial infarction (MI).
Results: We analyzed the expression of 365 human miRs in plasma from healthy donors (n=9) and patients (n=11) with acute MI and ST-segment elevation (STEMI). In STEMI patients, during the initial 1 to 7 hours after the onset of MI symptoms, miR 1, 133a, 133b and 499 plasma levels increased over 10–190-folds (p<0.05) and at day 5 they were back to control values; in contrast, miR 122 and miR 375, at day 0 exhibited a 60 and 80 % decrease, respectively, and at day 30 they were still 50% lower than control (p<0.05). In 4 additional MI patients miR plasma levels were measured simultaneously and in the same blood samples with total CPK and TnI, at frequent intervals after reaching the hospital. All patients were reperfused within 4 hours after admission to the hospital. Both CPK and TnI had their peak expression 6 hours after reaching the hospital; in contrast miR 1, 133a and 133b peak increase was achieved within 3h whereas miR 499 peak occurred at 12 hours. Additional studies were performed in a mouse model of MI and miR plasma levels were measured at a single time point, i.e. 3 hr after coronary artery occlusion. Experiments in sham operated control (n=4) and MI (n=9) mice showed that circulating miR 1, 133a, 133b and 499 increased 10–18 folds (p< 0.01); this miR signature closely mimicked the results in humans.
Conclusions: miR 1, 133a, 133b and 499 plasma levels are strongly upregulated after MI and may represent novel and sensitive biomarkers of cardiac damage. The negative regulation of miR 122 and 375 observed in humans raises the possibility that in man, during severe cardiac ischemia, miR release from cardiac cells may be due also to the modulation of active transport mechanisms and not only to cardiac necrosis.