CHARACTERIZATION AND CHANGES OF GLYCOSPHINGOLIPIDS IN THE AORTA OF THE WATANABE HEREDITABLE HYPERLIPIDEMIC RABBIT
CHARACTERIZATION AND CHANGES OF GLYCOSPHINGOLIPIDS IN THE AORTA OF THE WATANABE HEREDITABLE HYPERLIPIDEMIC RABBIT
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DOI：
10.1093/oxfordjournals.jbchem.a123478
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发表时间：
1991-06-01
影响因子：
2.7
通讯作者：
TAKETOMI, T
中科院分区：
文献类型：
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作者：
HARA, A;TAKETOMI, T
本研究以Watanabe遗传性高胆固醇血症（WHHL）家兔为动物模型，观察了主动脉鞘糖脂沿着动脉粥样硬化的变化，并与正常家兔进行了比较。 正常和WHHL家兔脑组织中性鞘糖脂均由葡萄糖神经酰胺、半乳糖神经酰胺、乳糖神经酰胺、球三糖神经酰胺、球四糖神经酰胺和半乳糖新乳糖四糖神经酰胺组成。 WHHL兔主动脉中中性鞘糖脂的总量（557 nmol/g组织）比正常水平（107 nmol/g组织）增加约5倍。 观察到葡萄糖神经酰胺（正常水平的13倍）和乳糖神经酰胺（正常水平的12倍）显著增加。 WHHL兔主动脉中神经节苷脂总量（207 μ g NeuAc/g组织）显著增加，约为正常水平（17 μ g NeuAc/g组织）的12倍。 GM 3神经节苷脂比正常增加约11倍。 GD 3神经节苷脂在正常主动脉中几乎检测不到，在WHHL兔中也显示出显著增加（51.7 μ g NeuAc/g组织）。 在正常兔主动脉中不存在的硫脂在WHHL兔的主动脉中显著积累（280 nmol/g组织）。 WHHL兔中性鞘糖脂的脂肪酸组成中含有较多的C23：0，这是血清脂蛋白中糖脂的主要脂肪酸。 WHHL兔主动脉神经节苷脂中C16：0含量高于正常兔。 在WHHL兔主动脉中，硫苷鞘氨醇由鞘氨醇（86%）、二氢鞘氨醇（9%）、4-D-羟基二氢鞘氨醇（4%）和4-D-羟基二十碳鞘氨醇（小于1%）组成。 对WHHL兔主动脉鞘糖脂脂肪酸组成的分析结果表明，随着动脉粥样硬化的进展，主要来源于血清脂蛋白的各种鞘糖脂在WHHL兔主动脉中积累，并大部分水解为极性较小的糖脂，如葡萄糖神经酰胺或乳糖神经酰胺。 另一方面，作为正常主动脉的常见成分，神经酰胺三己糖、神经酰胺四己糖和神经酰胺半乳糖基新乳糖四己糖的中度增加表明WHHL家兔主动脉内膜显著增厚。 这也表明，GM 3和GD 3神经节苷脂不仅来自血清，而且还来自新型细胞群，如泡沫细胞或巨噬细胞在动脉粥样硬化病变，因为这些神经节苷脂的脂肪酸包括更多的棕榈酸比那些血清脂蛋白或正常主动脉。 最有趣的发现是，硫苷脂和GD 3神经节苷脂在WHHL兔的主动脉中的出现可能是动脉粥样硬化进展程度的有用指标，因为这些鞘糖脂在正常主动脉中几乎检测不到。
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-mu-g NeuAc/g tissue) was markedly increased, being about 12-fold the normal level (17-mu-g 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-mu-g 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%). The results of fatty acid analysis of glycosphingolipids in the aorta of WHHL rabbit suggested that the various glycosphingolipids mostly derived from serum lipoproteins were accumulated in the aorta of the WHHL rabbit along with the progression of atherosclerosis, and that most of these glycolipids were hydrolyzed into less polar glycolipids such as glucosylceramide or lactosylceramide. On the other hand, the moderate increases in globotriaosylceramide, globotetraosylceramide, and galactosylneolactotetraosylceramide, which are ordinary constituents of the normal aorta, indicated the marked intimal thickening of the aorta of the WHHL rabbit. It is also suggested that GM3 and GD3 gangliosides were derived not only from sera but also from new-type cell populations, such as foam cells or macrophages in the atherosclerotic lesions, because the fatty acids of these gangliosides included more palmitic acid than those of either serum lipoproteins or the normal aorta. The most interesting finding was that the occurrence of sulfatide and GD3 ganglioside in the aorta of the WHHL rabbit could be a useful indicator of the degree of progression of atherosclerosis, since these glycosphingolipids were hardly detected in the normal aorta.