Circulating MicroRNA-208b and MicroRNA-499 Reflect Myocardial Damage in Cardiovascular Disease

Abstract

Background-Small RNA molecules, called microRNAs, freely circulate in human plasma and correlate with varying pathologies. In this study, we 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: (1) acute myocardial infarction, (2) viral myocarditis, (3) diastolic dysfunction, and (4) acute heart failure. Plasma levels of selected microRNAs, including heart-associated (miR-1, -133a, -208b, and -499), fibrosisassociated (miR-21 and miR-29b), and leukocyte-associated (miR-146, -155, and -223) candidates, were subsequently assessed using real-time polymerase chain reaction. Strikingly, in plasma from acute myocardial infarction patients, cardiac myocyte-associated miR-208b and -499 were highly elevated, 1600-fold (PϽ0.005) and 100-fold (PϽ0.0005), respectively, as compared with control subjects. Receiver operating characteristic curve analysis revealed an area under the curve of 0.94 (PϽ10 Ϫ10 ) for miR-208b and 0.92 (PϽ10 Ϫ9 ) for miR-499. Both microRNAs correlated with plasma troponin T, indicating release of microRNAs from injured cardiomyocytes. In viral myocarditis, we observed a milder but significant elevation of these microRNAs, 30-fold and 6-fold, respectively. Plasma levels of leukocyte-expressed microRNAs were not significantly increased in acute myocardial infarction or viral myocarditis patients, despite elevated white blood cell counts. In patients with acute heart failure, only miR-499 was significantly elevated (2-fold), whereas 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, sex, body mass index, 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. (Circ Cardiovasc Genet. 2010;3:499-506.)

Comparative RNA-sequencing analysis of myocardial and circulating small RNAs in human heart failure and their utility as biomarkers

“…Increases in circulating miRNAs upon cell damage have been detected by RT-PCR-based approaches for liver, brain, and skeletal muscle (5), as well as heart (19,46 instances miRNAs even performed better than established protein biomarkers (5). Our analysis indicated that heart-specific myomirs performed similar to the highly sensitive cTnI assay, but we were unable to verify the utility of any recently proposed miRNA biomarker for HF (18,(20)(21)(22).…”

“…S1) were shown to contribute to muscle or myocardial function (8, 9). miRNAs and other classes of RNA have been profiled in failing human myocardium (10)(11)(12)(13)(14)(15)(16)(17), and a selected subset was also investigated as circulating biomarkers in HF (18)(19)(20)(21)(22)(23)(24). However, in these studies heart tissue and circulating miRNA abundance changes were not acquired simultaneously to correlate changes in tissue versus circulating miRNA composition.…”

MicroRNA and Its Role in Cardiovascular Disease

“…However, leukocyte specific miRNAs were not increased in significant amount [60]. Further to this, the role of miR-499 in AMI diagnosis has been supported by Adachi et al in which they measured the plasma concentration of miR-499 in 14 patients with acute coronary syndrome, 15 patients with congestive heart failure (CHF) and 10 patients without any cardiovascular disease.…”

Exercício físico e microRNAs: novas fronteiras na insuficiência cardíaca

“…There was an increase of more than 1,000-fold in acute myocardial infarction 6,[37][38][39] of miRs-208b and-499. In this condition, they reflect tissue injury and cell death.…”