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rdf:type |
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lifeskim:mentions |
umls-concept:C0023516,
umls-concept:C0031437,
umls-concept:C0127400,
umls-concept:C0134835,
umls-concept:C0205217,
umls-concept:C0271510,
umls-concept:C0282554,
umls-concept:C0332294,
umls-concept:C0870432,
umls-concept:C1135918,
umls-concept:C1555465,
umls-concept:C1705417
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pubmed:issue |
6
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pubmed:dateCreated |
2004-4-2
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pubmed:abstractText |
Leukocyte recruitment is crucial for the response to vascular injury in spontaneous and accelerated atherosclerosis. Whereas the mechanisms of leukocyte adhesion to endothelium or matrix-bound platelets have been characterized, less is known about the proadhesive role of smooth muscle cells (SMCs) exposed after endothelial denudation. In laminar flow assays, neointimal rat SMCs (niSMCs) supported a 2.5-fold higher arrest of monocytes and "memory" T lymphocytes than medial SMCs, which was dependent on both P-selectin and VLA-4, as demonstrated by blocking antibodies. The increase in monocyte arrest on niSMCs was triggered by the CXC chemokine GRO-alpha and fractalkine, whereas "memory" T cell arrest was mediated by stromal cell-derived factor (SDF)-1alpha. This functional phenotype was paralleled by a constitutively increased mRNA and surface expression of P-selectin and of relevant chemokines in niSMCs, as assessed by real-time PCR and flow cytometry. The increased expression of P-selectin in niSMCs versus medial SMCs was associated with enhanced NF-kappaB activity, as revealed by immunofluorescence staining for nuclear p65 in vitro. Inhibition of NF-kappaB by adenoviral IkappaBalpha in niSMCs resulted in a marked reduction of increased leukocyte arrest in flow. Furthermore, P-selectin expression by niSMCs in vivo was confirmed in a hypercholesterolemic mouse model of vascular injury by double immunofluorescence and by RT-PCR after laser microdissection. In conclusion, we have identified a NF-kappaB-mediated proinflammatory phenotype of niSMCs that is characterized by increased P-selectin and chemokine expression and thereby effectively supports leukocyte recruitment.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Apolipoproteins E,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CX3CL1,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, CX3C,
http://linkedlifedata.com/resource/pubmed/chemical/Cx3cl1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cx3cl1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Integrin alpha4beta1,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappaB inhibitor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/P-Selectin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-8B,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1524-4571
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
2
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pubmed:volume |
94
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
776-84
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:14963004-Animals,
pubmed-meshheading:14963004-Aorta, Thoracic,
pubmed-meshheading:14963004-Apolipoproteins E,
pubmed-meshheading:14963004-Arteriosclerosis,
pubmed-meshheading:14963004-Cell Adhesion,
pubmed-meshheading:14963004-Cells, Cultured,
pubmed-meshheading:14963004-Chemokine CX3CL1,
pubmed-meshheading:14963004-Chemokines, CX3C,
pubmed-meshheading:14963004-Chemotaxis, Leukocyte,
pubmed-meshheading:14963004-Constriction, Pathologic,
pubmed-meshheading:14963004-Cytokines,
pubmed-meshheading:14963004-Endothelium, Vascular,
pubmed-meshheading:14963004-Gene Expression Regulation,
pubmed-meshheading:14963004-Hypercholesterolemia,
pubmed-meshheading:14963004-I-kappa B Proteins,
pubmed-meshheading:14963004-Inflammation,
pubmed-meshheading:14963004-Integrin alpha4beta1,
pubmed-meshheading:14963004-Membrane Proteins,
pubmed-meshheading:14963004-Mice,
pubmed-meshheading:14963004-Mice, Knockout,
pubmed-meshheading:14963004-Monocytes,
pubmed-meshheading:14963004-Muscle, Smooth, Vascular,
pubmed-meshheading:14963004-Myocytes, Smooth Muscle,
pubmed-meshheading:14963004-NF-kappa B,
pubmed-meshheading:14963004-P-Selectin,
pubmed-meshheading:14963004-Rats,
pubmed-meshheading:14963004-Rats, Sprague-Dawley,
pubmed-meshheading:14963004-Receptors, Interleukin-8B,
pubmed-meshheading:14963004-Recombinant Fusion Proteins,
pubmed-meshheading:14963004-Recurrence,
pubmed-meshheading:14963004-Rheology,
pubmed-meshheading:14963004-T-Lymphocyte Subsets
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pubmed:year |
2004
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pubmed:articleTitle |
Neointimal smooth muscle cells display a proinflammatory phenotype resulting in increased leukocyte recruitment mediated by P-selectin and chemokines.
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pubmed:affiliation |
Department of Molecular Cardiovascular Research, University of Technology, Aachen, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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