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Journal of Molecular Medicine

, Volume 78, Issue 4, pp 217–227 | Cite as

Endogenous apolipoprotein E modulates cholesterol efflux and cholesteryl ester hydrolysis mediated by high-density lipoprotein-3 and lipid-free apolipoproteins in mouse peritoneal macrophages

  • Claus Langer
  • Yadong Huang
  • Paul Cullen
  • Bernd Wiesenhütter
  • Robert W. Mahley
  • Gerd Assmann
  • Arnold von Eckardstein
Original Article

Abstract.

We investigated the effect of endogenous apolipoprotein (apo) E synthesis in mouse peritoneal macrophages on cholesterol efflux and intracellular cholesteryl ester hydrolysis mediated by high-density lipoprotein-3 (HDL3) and lipid-free apolipoproteins (apo). After loading with acetylated LDL (acLDL) peritoneal macrophages from wild-type (apoE+/+) and apoE-deficient (apoE–/–) mice were incubated with medium alone or with liposomes, HDL3, lipid-free apoA-I, or lipid-free apoE3. Cholesterol and cholesteryl esters in the cells and culture media were quantified by HPLC. Incubation of apoE+/+ or apoE–/– macrophages for 18 h with medium alone or with liposomes did not cause significant changes in cellular cholesterol. Addition of HDL3, apoA-I, or apoE3 to the medium led to significant cholesterol efflux, which was less efficient in apoE–/– macrophages than in apoE+/+ macrophages. HDL and lipid-free apolipoproteins were more effective in reducing the cellular content of cholesteryl esters of apoE+/+ macrophages than of apoE–/– macrophages, suggesting that endogenous apoE stimulates cholesteryl ester hydrolysis. The difference in the mass of cholesteryl esters was more pronounced for cholesteryl arachidonate and linoleate than for cholesteryl oleate or palmitate. Furthermore, in [14C]arachidonate labeling experiments cholesterol arachidonate hydrolysis was higher in apoE+/+ macrophages than in apoE–/– macrophages in the presence of cholesterol efflux mediated by HDL3 or apoA-I. In contrast, in the absence of cholesterol efflux cholesterol arachidonate synthesis was higher in apoE+/+ macrophages than in apoE–/– macrophages. Taken together, our data suggest that endogenous apoE stimulates cholesterol efflux and intracellular cholesteryl ester hydrolysis mediated by HDL3 and lipid-free apolipoproteins in mouse peritoneal macrophages. This may contribute to the antiatherogenic effect of apoE.

Apolipoprotein A-I Reverse cholesterol transport Atherosclerosis Arachidonic acid 

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Copyright information

© Springer-Verlag 2000

Authors and Affiliations

  • Claus Langer
    • 1
  • Yadong Huang
    • 3
  • Paul Cullen
    • 1
  • Bernd Wiesenhütter
    • 2
  • Robert W. Mahley
    • 3
  • Gerd Assmann
    • 1
  • Arnold von Eckardstein
    • 1
  1. 1.Institute of Arteriosclerosis Research, Domagkstrasse 3, 48149 Münster, GermanyGermany
  2. 2.Institute of Clinical Chemistry and Laboratory Medicine, Central Laboratory, Westphalian Wilhelms-University, Albert-Schweitzer-Strasse 33, 48129 Münster, GermanyGermany
  3. 3.Gladstone Institute of Cardiovascular Disease, POB 419100, San Francisco, CA 94141-9100, USAUSA

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