Characterization and changes of glycosphingolipids in the aorta of the Watanabe hereditable hyperlipidemic rabbit

Characterization and elucidation of the changes of glycosphingolipids in the aorta along with the progression of atherosclerosis were performed in the Watanabe hereditable hyperlipidemic (WHHL) rabbit, an animal model for human familial hypercholesterolemia, as compared with in the normal rabbit. Neutral glycosphingolipids in aortae of both normal and WHHL rabbits were composed of glucosylceramide, galactosylceramide, lactosylceramide, globotriaosylceramide, globotetraosylceramide, and galactosylneolactotetraosylceramide. The total amount of neutral glycosphingolipids in the aorta of the WHHL rabbit (557 nmol/g tissue) was increased about 5-fold compared to the normal level (107 nmol/g tissue). Prominent increases were observed in glucosylceramide (13-fold the normal level) and lactosylceramide (12-fold the normal level). The amount of total gangliosides in the aorta of the WHHL rabbit (207 micrograms NeuAc/g tissue) was markedly increased, being about 12-fold the normal level (17 micrograms NeuAc/g tissue). GM3 ganglioside was increased about 11-fold compared to normal. GD3 ganglioside, which was almost undetectable in normal aorta, also showed a marked increase in that of the WHHL rabbit (51.7 micrograms NeuAc/g tissue). Sulfatide, which was absent in the aorta of the normal rabbit, was markedly accumulated in that of the WHHL rabbit (280 nmol/g tissue). The fatty acid composition of neutral glycosphingolipids of WHHL rabbit was found to include a higher amount of C23:0, which is the major fatty acid of glycolipids in serum lipoproteins. Gangliosides in the aorta of the WHHL rabbit contained more C16:0 than in the normal rabbit. Sphingosine of sulfatide in the aorta of the WHHL rabbit was composed of sphingenine (86%), sphinganine (9%), 4-D-hydroxysphinganine (4%), and 4-D-hydroxyeicosasphinganine (less than 1%).(ABSTRACT TRUNCATED AT 250 WORDS)