MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins

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...

Full description

Saved in:
Bibliographic Details
Published in:Nature cell biology Vol. 13; no. 4; pp. 423 - 433
Main Authors: Vickers, Kasey C., Palmisano, Brian T., Shoucri, Bassem M., Shamburek, Robert D., Remaley, Alan T.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 01.04.2011
Nature Publishing Group
Subjects:
631/337/384/331
631/61/2300
Animals
Apolipoproteins E - genetics
Apolipoproteins E - metabolism
Atherosclerosis - blood
Atherosclerosis - genetics
Biological Transport - physiology
Biomarkers
Biomarkers - blood
Biomedical and Life Sciences
Cancer Research
Care and treatment
CD36 Antigens - genetics
CD36 Antigens - metabolism
Cell Biology
Chromatography
Communication
Developmental Biology
Diagnosis
Gene expression
Gene Expression Regulation
High density lipoprotein
High density lipoproteins
Humans
Hypercholesterolemia
Hyperlipoproteinemia Type II - blood
Hyperlipoproteinemia Type II - genetics
Life Sciences
Lipoproteins
Lipoproteins, HDL - blood
Mice
Mice, Knockout
MicroRNA
MicroRNAs
MicroRNAs - blood
Physiological aspects
Plasma
Proteins
Receptors, LDL - genetics
Receptors, LDL - metabolism
Stem Cells
United States
ISSN:1465-7392, 1476-4679, 1476-4679
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. Human high-density lipoprotein (HDL) is found to transport endogenous miRNAs in plasma and to deliver them to recipient cells where they can silence mRNA reporter targets. HDL miRNAs isolated from atherogenic mice models or human atherosclerotic subjects induce changes in gene expression different from the ones seen with control HDL–miRNA populations.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ObjectType-Article-2
ObjectType-Feature-1
ISSN:1465-7392
1476-4679
1476-4679
DOI:10.1038/ncb2210