Effect of macrophage-derived apolipoprotein E on hyperlipidemia and atherosclerosis of LDLR-deficient mice

Weibin Shi, Xuping Wang, Jack Wong, Catherine C. Hedrick, Howard Wong, Lawrence W. Castellani, Aldons J. Lusis

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


LDL receptor-deficient (LDLR-/-) mice fed a Western diet exhibit severe hyperlipidemia and develop significant atherosclerosis. Apolipoprotein E (apoE) is a multifunctional protein synthesized by hepatocytes and macrophages. We sought to determine effect of macrophage apoE deficiency on severe hyperlipidemia and atherosclerosis. Female LDLR-/- mice were lethally irradiated and reconstituted with bone marrow from either apoE -/- or apoE+/+ mice. Four weeks after transplantation, recipient mice were fed a Western diet for 8 weeks. Reconstitution of LDLR -/- mice with apoE-/- bone marrow resulted in a slight reduction in plasma apoE levels and a dramatic reduction in accumulation of apoE and apoB in the aortic wall. Plasma lipid levels were unaffected when mice had mild hyperlipidemia on a chow diet, whereas IDL/LDL cholesterol levels were significantly reduced when mice developed severe hyperlipidemia on the Western diet. The hepatic VLDL production rate of mice on the Western diet was decreased by 46% as determined by injection of Triton WR1339 to block VLDL clearance. Atherosclerotic lesions in the proximal aorta were significantly reduced, partially due to reduction in plasma total cholesterol levels (r=0.56;P<0.0001). Thus, macrophage apoE-deficiency alleviates severe hyperlipidemia by slowing hepatic VLDL production and consequently reduces atherosclerosis in LDLR-/- mice.

Original languageEnglish (US)
Pages (from-to)223-229
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number1
StatePublished - Apr 23 2004
Externally publishedYes


  • Apolipoprotein E
  • Atherosclerosis
  • Bone marrow transplantation
  • Hyperlipidemia
  • Macrophages

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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