title: Characterization of levels and cellular transfer of circulating lipoprotein-bound microRNAs.
abstract: OBJECTIVE
  MicroRNAs are important intracellular regulators of gene expression, but also circulate in the blood being protected by extracellular vesicles, proteins, or high-density lipoprotein (HDL). Here, we evaluate the regulation and potential function of HDL- and low-density lipoprotein-bound miRs isolated from healthy subjects and patients with coronary artery disease.
  
  
  RESULTS
  HDL-bound miRs with known effects in the cardiovascular system were analyzed in HDL isolated from healthy subjects (n=10), patients with stable coronary artery disease (n=10), and patients with an acute coronary syndrome (n=10). In HDL from healthy subjects, miR-223 was detected at concentrations >10 000 copies/µg HDL, and miR-126 and miR-92a at about 3000 copies/µg HDL. Concentrations of most miRs were substantially higher in HDL as compared with low-density lipoprotein. However, HDL-bound miR-223 contributed to only 8% of the total circulating miRs. The signatures of miRs varied only slightly in HDL derived from patients with coronary artery disease. We did not observe a significant uptake of HDL-bound miRs into endothelial cells, smooth muscle cells, or peripheral blood mononuclear cells. However, patient-derived HDL transiently reduced miR expression particularly when incubated with smooth muscle and peripheral blood mononuclear cells.
  
  
  CONCLUSIONS
  Circulating miRs are detected in HDL and to a lesser extent in low-density lipoprotein, and the miR-signatures are only slightly altered in patients with coronary artery disease. Lipoprotein-bound miRs were not efficiently delivered to endothelial, smooth muscle, and peripheral blood mononuclear cells suggesting that the lipoprotein-associated pool of miRs is not regulating the function of the studied cells in vitro.
authors.affiliation: Institute of Cardiovascular Regeneration, Centre for Molecular Medicine, Goethe-University Frankfurt, Frankfurt, Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Wagner
authors.forename: Meliana
authors.initials: M
authors.lastname: Riwanto
authors.forename: Christian
authors.initials: C
authors.lastname: Besler
authors.forename: Andrea
authors.initials: A
authors.lastname: Knau
authors.forename: Stephan
authors.initials: S
authors.lastname: Fichtlscherer
authors.forename: Tino
authors.initials: T
authors.lastname: Röxe
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Zeiher
authors.forename: Ulf
authors.initials: U
authors.lastname: Landmesser
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000503:physiopathology; D016022:Case-Control Studies; D002478:Cells, Cultured; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000097:blood / Q000378:metabolism; D003324:Coronary Artery Disease / Q000097:blood* / Q000503:physiopathology; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000378:metabolism*; D008875:Middle Aged; D011237:Predictive Value of Tests; D012016:Reference Values; D012680:Sensitivity and Specificity
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008074:Lipoproteins; D035683:MicroRNAs
keywords: cardiovascular disease; circulation; endothelial cells; high-density lipoprotein; microRNA