GLYCOSPHINGOLIPID ACCUMULATION IN THE AORTIC-WALL IS ANOTHER FEATURE OF HUMAN ATHEROSCLEROSIS

High accumulation of lipids is a typical feature of an atherosclerotic lesion. We have previously identified the chemical structure of the m ajor glycosphingolipids (GSLs) of human aorta; however, quantification of the absolute concentration of GSLs was not carried out. In the pre sent study, for the first time we have performed a quantitative compar ative analysis of GSL composition in the media and two sublayers of th e intima taken from normal regions, fatty streaks, and atherosclerotic plaques of the human aorta. The intimal tissue containing fatty strea ks and atherosclerotic plaques accumulated GSLs, predominantly glucosy lceramide (GlcCer), lactosylceramide (LacCer), and ganglioside G(M3). GSL levels in plaques were highest: GlcCer was 18- and 8-fold, LacCer was 8- and 7-fold, and G(M3) was 2.5- and 12-fold higher than in muscu loelastic and elastic-hyperplastic intimal layers of normal regions, r espectively. We did not observe a significant increase in other GSLs. An increase in the content of gangliosides G(D3) and G(D1a) was detect ed in the media underlying atherosclerotic lesions. On the basis of an analysis of the ratio of GlcCer, LacCer, and G(M3); accumulated in th e tissue and cells of the elastic-hyperplastic layer of intima, we hav e concluded that the accumulation of the above-mentioned GSLs occurs m ainly in the extracellular space of the intima. In this study, we have also demonstrated that extracellular lipid liposomes, which appear in the early stages of atherogenesis, are one locus of GSL accumulation in the extracellular space of the intima. The findings suggest that th e GSL concentration and distribution within the normal and atheroscler otic aorta reflects a number of factors that include (1) synthesis of GSLs within the vessel wall, (2) deposition of GSLs within the vessel wall from plasma-derived lipoproteins, (3) the degree of association o f the various GSLs with intimal cells as well as extracellular lipid p articles, and (4) metabolic relationships between cholesterol and GSL accumulation.