Macrophages, inflammation, and atherosclerosis

MacRae F. Linton, Sergio Fazio

Research output: Contribution to journalArticle

200 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalInternational Journal of Obesity
Volume27
Issue numberSUPPL. 3
DOIs
StatePublished - Dec 2003
Externally publishedYes

Fingerprint

atherosclerosis
Atherosclerosis
macrophages
inflammation
Macrophages
Inflammation
foam cells
Foam Cells
monocytes
Tunica Intima
Monocytes
fatty acid-binding proteins
Fatty Acid-Binding Proteins
cholesteryl esters
Cholesterol Esters
LDL Receptors
Cholesterol
cholesterol
Apolipoproteins E
low density lipoprotein

Keywords

  • ACAT
  • aP2
  • apoE
  • Atherosclerosis
  • COX
  • Cytokine
  • Macrophage
  • Monocytes

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Public Health, Environmental and Occupational Health
  • Endocrinology
  • Food Science
  • Endocrinology, Diabetes and Metabolism

Cite this

Macrophages, inflammation, and atherosclerosis. / Linton, MacRae F.; Fazio, Sergio.

In: International Journal of Obesity, Vol. 27, No. SUPPL. 3, 12.2003.

Research output: Contribution to journalArticle

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