Cardiovascular extracellular microRNAs: emerging diagnostic markers and mechanisms of cell-to-cell RNA communication

Abstract

Cardiovascular diseases are a leading cause of morbidity and mortality in Western societies. It is now well established that microRNAs (miRNAs) are determinant regulators in various medical conditions including cardiovascular diseases. The recent discovery that miRNAs, while associated with different carriers, can be exported out of the cell, has triggered a renewed interest to analyze the potential to use extracellular miRNAs as tools for diagnostic and therapeutic studies. Circulating miRNAs in biological fluids present a technological advantage compared to current diagnostic tools by virtue of their remarkable stability and relative ease of detection rendering them ideal tools for non-invasive and rapid diagnosis. Extracellular miRNAs also represent a novel form of inter-cellular communication by transferring genetic information from a donor cell to a recipient cell. This review briefly summarizes recent insights in the origin, function and diagnostic potential of extracellular miRNAs by focusing on a select number of cardiovascular diseases.

Keywords: biomarkers; cardiovascular diseases; extracellular microRNA; inter-cellular communications.

FIGURE 1

Schematic representation of cellular release (A) and inter-cellular communication (B) of miRNAs. (A) In the nucleus, miRNA genes are mainly transcribed by the RNA polymerase II (Pol II) into primary miRNAs (pri-miRNAs) and processed to precursor miRNAs (pre-miRNAs) by the Drosha complex. Pre-miRNAs are exported to the cytoplasm and cleaved by Dicer to produce a double stranded miRNA duplex. The duplex is separated and a mature miRNA is incorporated into the RNA-induced silencing complex (RISC) while the other strand is likely subject to degradation. Within the RISC complex, miRNAs bind to their target messenger RNAs (mRNAs) to repress their translation or induce their degradation. In addition, miRNAs can be exported out of the cells and transported by various carriers, membrane-derived vesicles (exosomes, microvesicles, apoptotic bodies), miRNA-binding protein complexes (RBP), or high density lipoproteins (HDL). (B) Extracellular miRNAs can be transferred to recipient cells where they alter gene expression.