Utility of circulating microRNAs as clinical biomarkers for cardiovascular diseases

Abstract

MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate gene and protein expression by translational repression and/or mRNA degradation. miRNAs are implicated in the pathogenesis of various cardiovascular diseases and have become potential targets for therapeutic intervention. Their stability and presence in variety of readily accessible cell types including whole blood, serum, plasma, and other body fluids render them as potential source of a clinical biomarker. This review provides a brief overview of miRNA biogenesis and function, the diagnostic potential of circulating extracellular miRNA and their specific role in vivo in various cardiovascular settings, and their future perspective as clinical biomarkers. It is clearly evident from experimental studies that miRNAs are responsible for the regulation of several biological functions and alterations in cardiovascular diseases. Current data supports the concept of using circulating miRNAs as a biomarker in cardiovascular disease. It remains to be seen, however, whether circulating miRNAs can fulfil this role to improve risk and severity prediction.

Figure 1

A simplified flow chart depicting the steps involved in intracellular biogenesis of miRNA and their secretion in circulation. It is hypothesized that the mature miRNA can be secreted outside the cell via (1) exosomes when multivesicular body fuses with the cell membrane, (2) miRNA-protein complexes (Argonaute 2, nucleoplasmin), (3) HDL-miRNA complexes, (4) apoptotic bodies or microvesicles through interaction with membrane proteins, and (5) free miRNAs by natural spill or as by-products of dead cells. Various tissues and blood cells can contribute to the circulating miRNA pool. In otherwise undetectable levels in circulation, cardiac-specific miRNAs are released into the bloodstream in response to injury, such as AMI, and may serve as biomarkers for cardiovascular diseases.