Circulating MicroRNAs as Biomarkers in Coronary Heart Disease and Heart Failure

Abstract

MicroRNAs (miRNAs) are small non-coding, single-stranded RNAs (19-25 nucleotides long) that regulate expression of multiple target genes, predominantly by binding to the 3' untranslated region of messenger RNA (mRNA) transcripts, resulting either in translational inhibition or mRNA degradation. miRNAs are found in many bodily fluids, including plasma and serum, and are protected from degradation in the circulation through association with lipids, proteins, or microparticles, making them attractive disease biomarker candidates. Circulating levels of cardiac miRNAs (including miR-1, miR-133a, miR-208a, miR-208b, and miR-499) have been frequently reported as elevated in both coronary heart disease (CHD) and heart failure (HF) and have been proposed as candidate biomarkers that reflect the severity of myocardial injury. Subsequent large, array-based screening studies comparing patients and controls have identified altered expression of additional miRNAs, not just those of cardiac origin. However, among these studies there has been little consensus as to which miRNAs are top candidates for diagnosis or prognosis in either CHD or HF. The measurement of circulating miRNAs is further complicated by the timing of collection, especially after acute cardiac events while miRNA levels in blood may be rapidly changing; confounding influences from medications or contaminating blood cells at the time of sampling; and the need for standardization of normalization strategies. This review evaluates recent developments in the identification of circulating miRNAs as markers for diagnosis and prognosis in CHD and HF, and the methodological issues in measurement of circulating miRNAs. Research Article