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J. Lipid Res.
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Journal of Lipid Research, Vol. 43, 205-214, February 2002
Copyright © 2002 by Lipid Research, Inc.

Increased glycosphingolipid levels in serum and aortae of apolipoprotein E gene knockout mice

Brett Garnera, David A. Priestmana, Roland Stockerb, David J. Harveya, Terry D. Buttersa, and Frances M. Platta
a Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
b Biochemistry Group, Heart Research Institute, Sydney, 2050 N.S.W., Australia

Correspondence to: Frances M. Platt, To whom correspondence should be addressed., fran{at}glycob.ox.ac.uk (E-mail)

The apolipoprotein E gene knockout (apoE-/-) mouse develops atherosclerosis that shares many features of human atherosclerosis. Increased levels of glycosphingolipid (GSL) have been reported in human atherosclerotic lesions; however, GSL levels have not been studied in the apoE-/- mouse. Here we used HPLC methods to analyze serum and aortic GSL levels in apoE-/- and C57BL/6J control mice. The concentrations of glucosyl ceramide (GlcCer), lactosyl ceramide (LacCer), GalNAcß1-4Galß1-4Glc-Cer (GA2), and ceramide trihexoside (CTH) were increased by approximately 7-fold in the apoE-/- mouse serum compared with controls. The major serum ganglioside, N-glycolyl GalNAcß1-4[NeuNAc{alpha}2-3]Galß1-4Glc-Cer (N-glycolyl GM2), was increased in concentration by approximately 3-fold. A redistribution of GSLs from HDL to VLDL populations was also observed in the apoE-/- mice. These changes were accompanied by an increase in the levels of GSLs in the aortic sinus and arch of the apoE-/- mice. The spectrum of gangliosides present in the aortic tissues was more complex than that found in the lipoproteins, with the latter represented almost entirely by N-glycolyl GM2 and the former comprised of NeuNAc{alpha}2-3Galß1-4Glc-Cer (GM3), GM2, N-glycolyl GM2, GM1, GD3, and GD1a.

In conclusion, neutral GSL and ganglioside levels were increased in the serum and aortae of apoE-/- mice compared with controls, and this was associated with a preferential redistribution of GSL to the proatherogenic lipoprotein populations. The apoE-/- mouse therefore represents a useful model to study the potential role of GSL metabolism in atherogenesis. — Garner, B., D. A. Priestman, R. Stocker, D. J. Harvey, T. D. Butters, and F. M. Platt. Increased glycosphingolipid levels in serum and aortae of apolipoprotein E gene knockout mice. J. Lipid Res. 2002. 43: 205–214.

Supplementary key words: apoE gene knockout, ganglioside analysis, atherosclerosis


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