Liver microRNAs: potential mediators and biomarkers for metabolic and cardiovascular disease?

Abstract

Recent discoveries have revealed that microRNAs (miRNAs) play a key role in the regulation of gene expression. In this review, we summarize the rapidly evolving knowledge about liver miRNAs (including miR-33, -33*, miR-223, -30c, -144, -148a, -24, -29, and -122) and their link to hepatic lipid metabolism, atherosclerosis and cardiovascular disease, non-alcoholic fatty liver disease, metabolic syndrome, and type-2 diabetes. With regards to its biomarker potential, the main focus is on miR-122 as the most abundant liver miRNA with exquisite tissue specificity. MiR-122 has been proposed to play a central role in the maintenance of lipid and glucose homeostasis and is consistently detectable in serum and plasma. This miRNA may therefore constitute a novel biomarker for cardiovascular and metabolic diseases.

Keywords: Biomarkers; Cardiovascular disease; Lipid metabolism; MicroRNAs.

Figure 1

Role of miR-122 in lipid homeostasis. ASO, antisense oligonucleotide; FA, fatty acid; HMGCR, 3-hydroxy-3-methylglutaryl-CoA reductase; KO, knock-out; LDL, low-density lipoprotein; LPL, lipoprotein lipase; LDLR, low-density lipoprotein receptor; MTP, microsomal triglyceride transfer protein; TG, triglycerides; VLDL, very-low-density lipoprotein.

Figure 2

Sources of circulating miRNAs. Circulating cells, in particular platelets, release miRNAs upon activation (i.e. miR-21, miR-24, miR-126, miR-191, and miR-223). Tissues release miRNAs upon injury; i.e. miR-1, miR-208, and miR-499 are elevated after myocardial infarction. The liver, however, constantly secretes miR-122. Unlike miR-122, other liver miRNAs are not tissue specific and not as abundant. Thus, most of them cannot be reliably detected in the circulation (Table 1).