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...

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Veröffentlicht in:	Nature cell biology Jg. 13; H. 4; S. 423 - 433
Hauptverfasser:	Vickers, Kasey C., Palmisano, Brian T., Shoucri, Bassem M., Shamburek, Robert D., Remaley, Alan T.
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London Nature Publishing Group UK 01.04.2011 Nature Publishing Group
Schlagworte:	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-Zugang:	Volltext
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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. 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.
AbstractList	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 mRNA reporters. Furthermore, HDL-mediated delivery of miRNAs to recipient cells was demonstrated to be scavenger receptor BI-dependent. The human HDL-miRNA profile from normal subjects is significantly different than 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 suggest that HDL participates in a mechanism of intercellular communication involving the transport and delivery of miRNAs. 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.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. 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. 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.
Audience	Academic
Author	Vickers, Kasey C. Palmisano, Brian T. Shamburek, Robert D. Shoucri, Bassem M. Remaley, Alan T.
AuthorAffiliation	1 National Heart, Lung and Blood Institute, National Institutes of Health, 10 Center Dr. Building 10 8N222, Bethesda, Maryland 20892, USA
AuthorAffiliation_xml	– name: 1 National Heart, Lung and Blood Institute, National Institutes of Health, 10 Center Dr. Building 10 8N222, Bethesda, Maryland 20892, USA
Author_xml	– sequence: 1 givenname: Kasey C. surname: Vickers fullname: Vickers, Kasey C. email: vickerskc@nhlbi.nih.gov organization: National Heart, Lung and Blood Institute, National Institutes of Health – sequence: 2 givenname: Brian T. surname: Palmisano fullname: Palmisano, Brian T. organization: National Heart, Lung and Blood Institute, National Institutes of Health – sequence: 3 givenname: Bassem M. surname: Shoucri fullname: Shoucri, Bassem M. organization: National Heart, Lung and Blood Institute, National Institutes of Health – sequence: 4 givenname: Robert D. surname: Shamburek fullname: Shamburek, Robert D. organization: National Heart, Lung and Blood Institute, National Institutes of Health – sequence: 5 givenname: Alan T. surname: Remaley fullname: Remaley, Alan T. organization: National Heart, Lung and Blood Institute, National Institutes of Health
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/21423178$$D View this record in MEDLINE/PubMed
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Snippet	Circulating microRNAs (miRNA) are relatively stable in plasma and are a new class of disease biomarkers. Here we present evidence that high-density lipoprotein...
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SubjectTerms	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
Title	MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins
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