Microparticles: major transport vehicles for distinct microRNAs in circulation

Abstract

AimsCirculating microRNAs (miRNAs) have attracted major interest as biomarkers for cardiovascular diseases. Since RNases are abundant in circulating blood, there needs to be a mechanism protecting miRNAs from degradation. We hypothesized that microparticles (MP) represent protective transport vehicles for miRNAs and that these are specifically packaged by their maternal cells.Methods and resultsConventional plasma preparations, such as the ones used for biomarker detection, are shown to contain substantial numbers of platelet-, leucocyte-, and endothelial cell-derived MP. To analyse the widest spectrum of miRNAs, Next Generation Sequencing was used to assess miRNA profiles of MP and their corresponding stimulated and non-stimulated cells of origin. THP-1 (monocytic origin) and human umbilical vein endothelial cell (HUVEC) MP were used for representing circulating MP at a high purity. miRNA profiles of MP differed significantly from those of stimulated and non-stimulated maternal THP-1 cells and HUVECs, respectively. Quantitative reverse transcription–polymerase chain reaction of miRNAs which have been associated with cardiovascular diseases also demonstrated significant differences in miRNA profiles between platelets and their MP. Notably, the main fraction of miRNA in plasma was localized in MP. Furthermore, miRNA profiles of MP differed significantly between patients with stable and unstable coronary artery disease.ConclusionCirculating MP represent transport vehicles for large numbers of specific miRNAs, which have been associated with cardiovascular diseases. miRNA profiles of MP are significantly different from their maternal cells, indicating an active mechanism of selective ‘packaging’ from cells into MP. These findings describe an interesting mechanism for transferring gene-regulatory function from MP-releasing cells to target cells via MP circulating in blood.

Microvesicles and diabetic complications — novel mediators, potential biomarkers and therapeutic targets

“…MVs isolated from patients with atherosclerosis contain higher levels of miR-150 and can promote human microvascular endothelial cell-1 (HMEC-1) cell migration, compared with MVs from healthy controls [93] . These findings suggest selective transport of miRNA into MVs under certain pathophysiological conditions [26] . There is increasing evidence for the potential use of specific endothelial-derived MV-associated miRNA signatures in body fluids or particularly in peripheral blood as biomarkers to predict metabolic diseases [94] .…”

“…Several miRNAs are present in MVs involved in CAD and diabetes, such as miR-126, miR-21, and miR-29 [91,92] . The miRNA profiles of MVs differ significantly between patients with stable and unstable CAD and between stimulated and non-stimulated cultured cells in vitro [26] . MVs isolated from patients with atherosclerosis contain higher levels of miR-150 and can promote human microvascular endothelial cell-1 (HMEC-1) cell migration, compared with MVs from healthy controls [93] .…”

“…Recent studies demonstrated that MVs represent protective transport vehicles for microRNAs that are specifically packaged by their parental cells [26] . As potential diagnostic and prognostic biomarkers, standardized methodologies for measuring MVs in human samples are still not available.…”

Microparticles and their Roles in Inflammation: A Review§

“…Study on MP derived from monocytic leukaemia cell line THP-1 showed that by transferring miRNAs (e.g. miRNA-320) to cardiac cells, they can exert their proinflammatory effects by altering gene expression directly [68]. Compared to non-stimulated THP-derived MP, miRNA-21 in stimulated THP-derived MP is one of the highest to be up-regulated among other miRNAs.…”

“…Examples of miRNAwhich exert anti-inflammatory effects are; miRNA-126, which inhibits VCAM-1 [70] and is found decreased in CVD patients [41] and miRNA-431, an inhibitor of macrophage migration inhibitory factor (MIF), which has a cardioprotective effect in ischemia reperfusion injury [68].…”