Lack of Macrophage Fatty-Acid-Binding Protein aP2 Protects Mice Deficient in Apolipoprotein E Against Atherosclerosis

Nat Med. 2001 Jun;7(6):699-705. doi: 10.1038/89076.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adipocytes / physiology*
  • Animals
  • Aorta / cytology
  • Apolipoproteins E / metabolism*
  • Arteriosclerosis / etiology
  • Arteriosclerosis / physiopathology*
  • Arteriosclerosis / prevention & control
  • Bone Marrow Transplantation
  • Carrier Proteins / metabolism*
  • Cell Line
  • Cholesterol Esters / metabolism
  • Diet
  • Fatty Acid-Binding Protein 7
  • Fatty Acid-Binding Proteins
  • Female
  • Foam Cells / physiology
  • Glucose / metabolism
  • Humans
  • Insulin / metabolism
  • Interleukin-1 / genetics
  • Interleukin-1 / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Lipids / blood
  • Macrophages / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neoplasm Proteins*
  • Nerve Tissue Proteins*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Suppressor Proteins*

Substances

  • Apolipoproteins E
  • Carrier Proteins
  • Cholesterol Esters
  • FABP7 protein, human
  • Fabp5 protein, mouse
  • Fabp7 protein, mouse
  • Fatty Acid-Binding Protein 7
  • Fatty Acid-Binding Proteins
  • Insulin
  • Interleukin-1
  • Interleukin-6
  • Lipids
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Tumor Necrosis Factor-alpha
  • Tumor Suppressor Proteins
  • Glucose