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 Mold. 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.-Gamer, 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.