Journal
CARDIOVASCULAR RESEARCH
Volume 93, Issue 4, Pages 633-644Publisher
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvs007
Keywords
MicroRNA; Microparticles; Vascular inflammation
Categories
Funding
- National Health and Medical Research Council (NHMRC) of Australia
- German Research Foundation (DFG)
- Monash University, Melbourne
- Australian Research Council
- German Heart Foundation
- Juvenile Diabetes Research Foundation International (JDRF)
- Diabetes Australia Research Trust (DART)
- National Health and Medical Research Council (NHMRC)
- National Heart Foundation of Australia (NHF)
- Baker IDI, Heart & Diabetes Institute, Melbourne, Australia
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Circulating 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. Conventional 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 transcriptionpolymerase 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. Circulating 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 opackaging' 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.
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