PMID- 14704742
OWN - NLM
STAT- MEDLINE
DCOM- 20040212
LR  - 20220331
VI  - 27 Suppl 3
DP  - 2003 Dec
TI  - Macrophages, inflammation, and atherosclerosis.
PG  - S35-40
AB  - 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.
FAU - Linton, MacRae F
AU  - Linton MF
AD  - Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 
      37232-6300, USA. macrae.linton@vanderbilt.edu
FAU - Fazio, Sergio
AU  - Fazio S
LA  - eng
GR  - HL-53989/HL/NHLBI NIH HHS/United States
GR  - HL57986/HL/NHLBI NIH HHS/United States
GR  - HL65405-01/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - England
TA  - Int J Obes Relat Metab Disord
JT  - International journal of obesity and related metabolic disorders : journal of the 
      International Association for the Study of Obesity
JID - 9313169
RN  - 0 (Carrier Proteins)
RN  - 0 (FABP7 protein, human)
RN  - 0 (Fabp5 protein, mouse)
RN  - 0 (Fabp7 protein, mouse)
RN  - 0 (Fatty Acid-Binding Protein 7)
RN  - 0 (Fatty Acid-Binding Proteins)
RN  - 0 (Isoenzymes)
RN  - 0 (Membrane Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (PTGS2 protein, human)
RN  - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
SB  - IM
MH  - Animals
MH  - Arteriosclerosis/*etiology/physiopathology
MH  - Carrier Proteins/physiology
MH  - Cyclooxygenase 2
MH  - Fatty Acid-Binding Protein 7
MH  - Fatty Acid-Binding Proteins
MH  - Humans
MH  - Inflammation/*complications
MH  - Isoenzymes/physiology
MH  - Macrophages/*physiology
MH  - Membrane Proteins
MH  - Mice
MH  - *Neoplasm Proteins
MH  - *Nerve Tissue Proteins
MH  - Prostaglandin-Endoperoxide Synthases/physiology
MH  - *Tumor Suppressor Proteins
RF  - 39
EDAT- 2004/01/06 05:00
MHDA- 2004/02/13 05:00
CRDT- 2004/01/06 05:00
PHST- 2004/01/06 05:00 [pubmed]
PHST- 2004/02/13 05:00 [medline]
PHST- 2004/01/06 05:00 [entrez]
AID - 0802498 [pii]
AID - 10.1038/sj.ijo.0802498 [doi]
PST - ppublish
SO  - Int J Obes Relat Metab Disord. 2003 Dec;27 Suppl 3:S35-40. doi: 
      10.1038/sj.ijo.0802498.