title: MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins.
abstract: Circulating microRNAs (miRNA) are relatively stable in plasma and are a new class of disease biomarkers. Here we present evidence that high-density lipoprotein (HDL) transports endogenous miRNAs and delivers them to recipient cells with functional targeting capabilities. Cellular export of miRNAs to HDL was demonstrated to be regulated by neutral sphingomyelinase. Reconstituted HDL injected into mice retrieved distinct miRNA profiles from normal and atherogenic models. HDL delivery of both exogenous and endogenous miRNAs resulted in the direct targeting of messenger RNA reporters. Furthermore, HDL-mediated delivery of miRNAs to recipient cells was demonstrated to be dependent on scavenger receptor class B type I. The human HDL-miRNA profile of normal subjects is significantly different from that of familial hypercholesterolemia subjects. Notably, HDL-miRNA from atherosclerotic subjects induced differential gene expression, with significant loss of conserved mRNA targets in cultured hepatocytes. Collectively, these observations indicate that HDL participates in a mechanism of intercellular communication involving the transport and delivery of miRNAs.
authors.affiliation: National Heart, Lung and Blood Institute, National Institutes of Health, 10 Center Dr. Building 10 8N222, Bethesda, Maryland 20892, USA. vickerskc@nhlbi.nih.gov
authors.forename: Kasey C
authors.initials: KC
authors.lastname: Vickers
authors.forename: Brian T
authors.initials: BT
authors.lastname: Palmisano
authors.forename: Bassem M
authors.initials: BM
authors.lastname: Shoucri
authors.forename: Robert D
authors.initials: RD
authors.lastname: Shamburek
authors.forename: Alan T
authors.initials: AT
authors.lastname: Remaley
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics; D001692:Biological Transport / Q000502:physiology*; D015415:Biomarkers / Q000097:blood; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000235:genetics; D008075:Lipoproteins, HDL / Q000097:blood*; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000097:blood*; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D018955:CD36 Antigens; D008075:Lipoproteins, HDL; D035683:MicroRNAs; D011973:Receptors, LDL