Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-2-15
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.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-10559140, http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-10779363, http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-11057902, http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-11701621, http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-12067907, http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-12615695, http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-12809600, http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-15459768, http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-15774908, http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-16121194, http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-16340955, http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-16397141, http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-16397142, http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-16943386, http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-17200718, http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-17283261, http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-17328047, http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-18451332, http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-18467644, http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-18576354, http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-18664460, http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-18927212, http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-19168526, http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-8299934, http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-8791534, http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-9326641, http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-9501202, http://linkedlifedata.com/resource/pubmed/commentcorrection/21242297-9759503
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1540-9538
pubmed:author
pubmed:issnType
Electronic
pubmed:day
14
pubmed:volume
208
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
217-25
pubmed:dateRevised
2011-8-25
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Growth differentiation factor 15 deficiency protects against atherosclerosis by attenuating CCR2-mediated macrophage chemotaxis.
pubmed:affiliation
Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, Netherlands. s.de.jager@lacdr.leidenuniv.nl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't