rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2011-2-15
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pubmed:abstractText |
Growth differentiation factor (GDF) 15 is a member of the transforming growth factor ? (TGF-?) superfamily, which operates in acute phase responses through a currently unknown receptor. Elevated GDF-15 serum levels were recently identified as a risk factor for acute coronary syndromes. We show that GDF-15 expression is up-regulated as disease progresses in murine atherosclerosis and primarily colocalizes with plaque macrophages. Hematopoietic GDF-15 deficiency in low density lipoprotein receptor(-/-) mice led to impaired initial lesion formation and increased collagen in later lesions. Although lesion burden in GDF-15(-/-) chimeras was unaltered, plaques had reduced macrophage infiltrates and decreased necrotic core formation, all features of improved plaque stability. In vitro studies pointed to a TGF?RII-dependent regulatory role of GDF-15 in cell death regulation. Importantly, GDF-15(-/-) macrophages displayed reduced CCR2 expression, whereas GDF-15 promoted macrophage chemotaxis in a strictly CCR2- and TGF?RII-dependent manner, a phenomenon which was not observed in G protein-coupled receptor kinase 2(+/-) macrophages. In conclusion, GDF-15 deletion has a beneficial effect both in early and later atherosclerosis by inhibition of CCR2-mediated chemotaxis and by modulating cell death. Our study is the first to identify GDF-15 as an acute phase modifier of CCR2/TGF?RII-dependent inflammatory responses to vascular injury.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-10559140,
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
|
pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1540-9538
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pubmed:author |
pubmed-author:AbiaRocioR,
pubmed-author:BermúdezBeatrizB,
pubmed-author:BiessenErik A LEA,
pubmed-author:BotIlzeI,
pubmed-author:BotMartineM,
pubmed-author:HeijnenCobi JCJ,
pubmed-author:KavelaarsAnnemiekeA,
pubmed-author:KoenenRory RRR,
pubmed-author:KuiperJohanJ,
pubmed-author:MurianaFrancisco J GFJ,
pubmed-author:SchilpMM,
pubmed-author:WeberChristianC,
pubmed-author:de JagerSaskia C ASC,
pubmed-author:de WaardVivianV,
pubmed-author:van BerkelTheo J CTJ
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pubmed:issnType |
Electronic
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pubmed:day |
14
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pubmed:volume |
208
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
217-25
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pubmed:dateRevised |
2011-8-25
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pubmed:meshHeading |
pubmed-meshheading:21242297-Animals,
pubmed-meshheading:21242297-Apoptosis,
pubmed-meshheading:21242297-Atherosclerosis,
pubmed-meshheading:21242297-Bone Marrow Transplantation,
pubmed-meshheading:21242297-Chemotaxis,
pubmed-meshheading:21242297-DNA Primers,
pubmed-meshheading:21242297-Flow Cytometry,
pubmed-meshheading:21242297-Gene Expression Regulation,
pubmed-meshheading:21242297-Growth Differentiation Factor 15,
pubmed-meshheading:21242297-Immunohistochemistry,
pubmed-meshheading:21242297-Macrophages,
pubmed-meshheading:21242297-Mice,
pubmed-meshheading:21242297-Mice, Knockout,
pubmed-meshheading:21242297-Phagocytosis,
pubmed-meshheading:21242297-Receptors, CCR2,
pubmed-meshheading:21242297-Receptors, LDL,
pubmed-meshheading:21242297-Reverse Transcriptase Polymerase Chain Reaction
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pubmed:year |
2011
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pubmed:articleTitle |
Growth differentiation factor 15 deficiency protects against atherosclerosis by attenuating CCR2-mediated macrophage chemotaxis.
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pubmed:affiliation |
Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, Netherlands. s.de.jager@lacdr.leidenuniv.nl
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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