Aims Circulating microRNAs have attracted major interest as biomarkers for cardiovascular diseases. Since RNases are abundant in circulating blood, there needs to be a mechanism protecting microRNAs from degradation. We hypothesized that microparticles represent protective transport vehicles for microRNAs and that these are specifically packaged by their maternal cells.
Methods&Results Conventional plasma preparations, such as the ones used for biomarker detection, are shown to contain substantial numbers of platelet-, leukocyte- and endothelial cell-derived microparticles. To analyze the widest spectrum of microRNAs, Next Generation Sequencing was used to assess microRNA-profiles of microparticles and their corresponding stimulated and non-stimulated cells of origin. THP-1 (monocytic origin) and human umbilical vein endothelial cell (HUVECs) microparticles were used for representing circulating microparticles at a high purity. MicroRNA-profiles of microparticles differed significantly from those of stimulated and non-stimulated maternal THP-1 cells and HUVECs, respectively. QRT-PCR of microRNAs which have been associated with cardiovascular diseases also demonstrated significant differences in miRNA-profiles between platelets and their microparticles. Notably, the main fraction of miRNA in plasma was localized in microparticles. Furthermore, microRNA-profiles of microparticles differed significantly between patients with stable and unstable coronary artery disease.
Conclusions Circulating microparticles represent transport vehicles for large numbers of specific microRNAs, which have been associated with cardiovascular diseases. MicroRNA-profiles of microparticles are significantly different from their maternal cells, indicating an active mechanism of selective “packaging” from cells into microparticles. These findings describe an interesting mechanism for transferring gene-regulatory function from microparticle-releasing cells to target cells via microparticles circulating in blood.
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PhilippDiehl, AlbaFricke, LauraSander, JohannesStamm, NicoleBassler, NayHtun, ThomasHelbing, AssamEl-Osta, Jeremy B. M.Jowett, KarlheinzPeterCardiovasc Res(2012)cvs007DOI: http://dx.doi.org/10.1093/cvr/cvs007First published online: 18 January 2012 cvs007