Abstract
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 language | English (US) |
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Pages (from-to) | 223-229 |
Number of pages | 7 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 317 |
Issue number | 1 |
DOIs | |
State | Published - Apr 23 2004 |
Externally published | Yes |
Keywords
- Apolipoprotein E
- Atherosclerosis
- Bone marrow transplantation
- Hyperlipidemia
- Macrophages
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology