Circulating MicroRNA-208b and MicroRNA-499 Reflect Myocardial Damage in Cardiovascular Disease.
- Cardiovascular Research Unit
BACKGROUND: -Small RNA molecules, called microRNAs, freely circulate in human plasma and correlate with varying pathologies. In this study, we have explored their diagnostic potential in a selection of prevalent cardiovascular disorders. METHODS AND RESULTS: -MicroRNAs were isolated from plasmas from well-characterized patients with varying degrees of cardiac damage: a) acute myocardial infarction (AMI), b) viral myocarditis (VM), c) diastolic dysfunction, and d) acute heart failure (AHF). Plasma levels of selected microRNAs, including heart-associated (miR-1, -133a, -208b and -499), fibrosis-associated (miR-21 and miR-29b) and leukocyte-associated (miR-146, -155 and -223) candidates, were subsequently assessed using real-time PCR. Strikingly, in plasma from AMI patients, cardiac myocyte-associated miRs-208b and -499 were highly elevated, 1600-fold (p<0.005) and 100-fold (p<0.0005) respectively, as compared with controls. ROC-curve analysis revealed an AUC of 0.94 (p<10(-10)) for miR-208b and 0.92 (p<10(-9)) for miR-499. Both microRNAs correlated with plasma troponin T, indicating release of microRNAs from injured cardiomyocytes. In VM, we observed a milder but significant elevation of these microRNAs, 30- and 6-fold respectively. Plasma levels of leukocyte-expressed microRNAs were not significantly increased in AMI or VM patients, despite elevated white blood cell counts. In AHF patients, only miR-499 was significantly elevated (2-fold), while no significant changes in microRNAs studied could be observed in diastolic dysfunction. Remarkably, plasma microRNA levels were not affected by a wide range of clinical confounders, including age, gender, BMI, kidney function, systolic blood pressure, and white blood cell count. CONCLUSIONS: -Cardiac damage initiates the detectable release of cardiomyocyte-specific microRNAs-208b and -499 into the circulation.