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

Abstract

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), GalNAcβ1-4Galβ1-4Glc-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 GalNAcβ1-4[NeuNAcα2-3]Galβ1-4Glc-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 NeuNAcα2-3Galβ1-4Glc-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.

Keywords

• apoE gene knockout
• ganglioside analysis
• atherosclerosis