Linked Life Data

14704742

Source:http://linkedlifedata.com/resource/pubmed/id/14704742

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2004-1-5
pubmed:abstractText
The macrophage plays a diverse array of roles in atherogenesis and lipoprotein metabolism. The macrophage functions as a scavenger cell, an immune mediator cell, and as a source of chemotactic molecules and cytokines. Chemokines have been implicated in promoting migration of monocytes into the arterial intima. Monocyte chemoattractant protein-1 (MCP-1) attracts monocytes bearing the chemokine receptor CCR-2. Macrophage expression of cyclooxygenase-2, a key enzyme in inflammation, promotes atherosclerotic lesion formation in low-density lipoprotein receptor (LDLR)-deficient mice. In the arterial intima, monocytes differentiate into macrophages, which accumulate cholesterol esters to form lipid-laden foam cells. Foam cell formation can be viewed as an imbalance in cholesterol homeostasis. The uptake of atherogenic lipoproteins is mediated by scavenger receptors, including SR-A and CD36. In the macrophage, ACAT-1 is responsible for esterifying free cholesterol with fatty acids to form cholesterol esters. Surprisingly, deficiency of macrophage ACAT-1 promotes atherosclerosis in LDLR-deficient mice. A number of proteins have been implicated in the process of promoting the efflux of free cholesterol from the macrophage, including apoE, ABCA1, and SRB-1. Macrophage-derived foam cells express the adipocyte fatty acid-binding protein (FABP), aP2, a cytoplasmic FABP that plays an important role in regulating systemic insulin resistance in the setting of obesity. ApoE-deficient mice null for macrophage aP2 expression develop significantly less atherosclerosis than controls wild type for macrophage aP2 expression. These results demonstrate a significant role for macrophage aP2 in the formation of atherosclerotic lesions independent of its role in systemic glucose and lipid metabolism. Furthermore, macrophages deficient in aP2 display alterations in inflammatory cytokine production. Through its distinct actions in adipocytes and macrophages, aP2 links features of the metabolic syndrome including insulin resistance, obesity, inflammation, and atherosclerosis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2, http://linkedlifedata.com/resource/pubmed/chemical/FABP7 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Fabp5 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Fabp7 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acid-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins, http://linkedlifedata.com/resource/pubmed/chemical/PTGS2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0307-0565
pubmed:author
pubmed:issnType
Print
pubmed:volume
27 Suppl 3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
S35-40
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Macrophages, inflammation, and atherosclerosis.
pubmed:affiliation
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-6300, USA. macrae.linton@vanderbilt.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review, Research Support, Non-U.S. Gov't