Increased glycosphingolipid levels in serum and aortae of apolipoprotein E gene knockout mice.
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), GalNAcbeta1-4Galbeta1-4Glc-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 GalNAcbeta1-4[NeuNAcalpha2-3]Galbeta1-4Glc-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 NeuNAcalpha2-3Galbeta1-4Glc-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
Brett
B
Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Priestman
David A
DA
Stocker
Roland
R
Harvey
David J
DJ
Butters
Terry D
TD
Platt
Frances M
FM
D000818:Animals; D001013:Aorta, Thoracic / Q000737:chemistry* / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D001161:Arteriosclerosis / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D006028:Glycosphingolipids / Q000097:blood* / Q000737:chemistry; D008074:Lipoproteins / Q000737:chemistry; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics / Q000378:metabolism; D012850:Sinus of Valsalva / Q000737:chemistry* / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D006028:Glycosphingolipids; D008074:Lipoproteins; D014280:Triglycerides; D002784:Cholesterol