HDL as a transporter of microRNAs in plasma: potential pathophysiolocal role

A. I. Gatsiou, K. Stellos, A. D. Tselepis



MicroRNAs (miRNAs, miRs) are small ribonucleic molecules which modulate the gene expression of their mRNA-targets. MiRNAs biogenesis initiates in the nucleus of the cell and is completed in the cytoplasm with the contribution of several enzymes. Binding of miRs into a multi-protein complex named RISC is required for their function. Circulating miRNAs are transported either bound in microparticles or as extracellular free molecules in complex with specific proteins. Recently, it has additionally been shown that an abundance of miRs array is bound on plasma HDL. However, the mechanism which mediates the uptake of miRs from HDL has not been elucidated yet. It has been shown though that ABCA1 receptor is important for the efflux of miRs to nascent HDL and that phosphatidylocholine may contribute to this process. Of interest, miRs are carried by HDL and delivered to recipient cells (e.g. hepatocytes) where miRs suppress the gene expression of their mRNAs-targets. As a result, miRs modulate the function of the recipient cells. This process is mediated by the scavenger receptor B1 (SRB1). Although, there are specific miRs detected exclusively or in higher concentrations in HDL from patients with familial hypercholesterolemia (FH), others are shown to be signatures miRs of HDL from healthy subjects. There are also commonly expressed HDL-bound miRs in healthy subjects and FH. A possible prognostic/diagnostic role of HDL-bound miRs as plasma biomarkers for disorders of lipoprotein metabolism and further for cardiovascular disease appears to emerges.

Keywords: Atherosclerosis, cardiovascular disease, HDL, lipoproteins, miRNAs