Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis.

Makowski L, Boord JB, Maeda K, Babaev VR, Uysal KT, Morgan MA, Parker RA, Suttles J, Fazio S, Hotamisligil GS, Linton MF
Nat Med. 2001 7 (6): 699-705

PMID: 11385507 · PMCID: PMC4027052 · DOI:10.1038/89076

The adipocyte fatty-acid-binding protein, aP2, has an important role in regulating systemic insulin resistance and lipid metabolism. Here we demonstrate that aP2 is also expressed in macrophages, has a significant role in their biological responses and contributes to the development of atherosclerosis. Apolipoprotein E (ApoE)-deficient mice also deficient for aP2 showed protection from atherosclerosis in the absence of significant differences in serum lipids or insulin sensitivity. aP2-deficient macrophages showed alterations in inflammatory cytokine production and a reduced ability to accumulate cholesterol esters when exposed to modified lipoproteins. Apoe-/- mice with Ap2+/+ adipocytes and Ap2-/- macrophages generated by bone-marrow transplantation showed a comparable reduction in atherosclerotic lesions to those with total aP2 deficiency, indicating an independent role for macrophage aP2 in atherogenesis. Through its distinct actions in adipocytes and macrophages, aP2 provides a link between features of the metabolic syndrome and could be a new therapeutic target for the prevention of atherosclerosis.

MeSH Terms (29)

Adipocytes Animals Aorta Apolipoproteins E Arteriosclerosis Bone Marrow Transplantation Carrier Proteins Cell Line Cholesterol Esters Diet Fatty Acid-Binding Protein 7 Fatty Acid-Binding Proteins Female Foam Cells Glucose Humans Insulin Interleukin-1 Interleukin-6 Lipids Macrophages Male Mice Mice, Inbred C57BL Mice, Transgenic Neoplasm Proteins Nerve Tissue Proteins Tumor Necrosis Factor-alpha Tumor Suppressor Proteins

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