title: Microparticles: major transport vehicles for distinct microRNAs in circulation.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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 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.
  
  
  CONCLUSIONS
  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 '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.
authors.affiliation: Atherothrombosis and Vascular Biology,  BakerIDI Heart and Diabetes Institute, 75 Commercial Road, Melbourne, VIC 3004,  Australia.
authors.forename: Philipp
authors.initials: P
authors.lastname: Diehl
authors.forename: Alba
authors.initials: A
authors.lastname: Fricke
authors.forename: Laura
authors.initials: L
authors.lastname: Sander
authors.forename: Johannes
authors.initials: J
authors.lastname: Stamm
authors.forename: Nicole
authors.initials: N
authors.lastname: Bassler
authors.forename: Nay
authors.initials: N
authors.lastname: Htun
authors.forename: Mark
authors.initials: M
authors.lastname: Ziemann
authors.forename: Thomas
authors.initials: T
authors.lastname: Helbing
authors.forename: Assam
authors.initials: A
authors.lastname: El-Osta
authors.forename: Jeremy B M
authors.initials: JB
authors.lastname: Jowett
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Peter
mesh_terms: D000368:Aged; D001692:Biological Transport / Q000502:physiology; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D055252:Cell-Derived Microparticles / Q000502:physiology*; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000097:blood* / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D012720:Severity of Illness Index; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D008070:Lipopolysaccharides; D035683:MicroRNAs; D013755:Tetradecanoylphorbol Acetate