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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2002-3-8
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pubmed:abstractText |
Leukotriene B4 (LTB4) is a potent chemotactic agent that activates monocytes through the LTB4 receptor (BLTR). We tested the hypothesis that LTB4 receptor blockade would slow atherosclerotic progression by inhibiting monocyte recruitment. Homozygous low-density receptor knockout (LDLr(-/-)) mice and apolipoprotein E deficient (apoE(-/-)) mice were treated with a specific LTB4 receptor antagonist, CP-105,696, for 35 days. In apoE(-/-)mice, treatment with the LTB4 antagonist did not affect plasma lipid concentrations but significantly reduced CD11b levels both in vascular lesions and whole blood. Compared with age-matched controls, lipid accumulation and monocyte infiltration were significantly reduced in treated apoE(-/-) mice at all time points tested. Lesion area reduction was also demonstrated in LDLr(-/-) mice maintained on a high-fat diet. LTB4 antagonism had no significant effect on lesion size in mice possessing the null alleles for another chemotactic agent, monocyte chemoattractant protein-1 (MCP-1(-/-)xapoE(-/-)), suggesting MCP-1 and LTB4 may either interact or exert their effects by a common mechanism. These results demonstrate that in a preclinical model of atherosclerosis LTB4 receptor blockade reduces lesion progression and further suggest a previously unrecognized role for LTB4 or other oxidized lipids recognized by the BLTR receptor in the pathogenesis of this disease.
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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/Benzopyrans,
http://linkedlifedata.com/resource/pubmed/chemical/CP 105696,
http://linkedlifedata.com/resource/pubmed/chemical/Carboxylic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Ccr2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL2,
http://linkedlifedata.com/resource/pubmed/chemical/Leukotriene Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Leukotriene B4,
http://linkedlifedata.com/resource/pubmed/chemical/Lipids,
http://linkedlifedata.com/resource/pubmed/chemical/Macrophage-1 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, CCR2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Chemokine,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, LDL,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Leukotriene B4
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1524-4636
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
22
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
443-9
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:11884288-Animals,
pubmed-meshheading:11884288-Apolipoproteins E,
pubmed-meshheading:11884288-Arteriosclerosis,
pubmed-meshheading:11884288-Benzopyrans,
pubmed-meshheading:11884288-Carboxylic Acids,
pubmed-meshheading:11884288-Chemokine CCL2,
pubmed-meshheading:11884288-Disease Progression,
pubmed-meshheading:11884288-Foam Cells,
pubmed-meshheading:11884288-Immunohistochemistry,
pubmed-meshheading:11884288-Leukotriene Antagonists,
pubmed-meshheading:11884288-Leukotriene B4,
pubmed-meshheading:11884288-Lipids,
pubmed-meshheading:11884288-Macrophage-1 Antigen,
pubmed-meshheading:11884288-Mice,
pubmed-meshheading:11884288-Mice, Inbred C57BL,
pubmed-meshheading:11884288-Mice, Knockout,
pubmed-meshheading:11884288-Monocytes,
pubmed-meshheading:11884288-Receptors, CCR2,
pubmed-meshheading:11884288-Receptors, Chemokine,
pubmed-meshheading:11884288-Receptors, LDL,
pubmed-meshheading:11884288-Receptors, Leukotriene B4
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pubmed:year |
2002
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pubmed:articleTitle |
Leukotriene B4 receptor antagonism reduces monocytic foam cells in mice.
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pubmed:affiliation |
Department of Cardiovascular and Metabolic Disease, Pfizer Global Research and Development, Groton, Conn 06340, USA. robert_j_aiello@groton.pfizer.com.
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pubmed:publicationType |
Journal Article
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