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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:1607-1615.)
© 1995 American Heart Association, Inc.

Articles

Glycosphingolipid Accumulation in the Aortic Wall Is Another Feature of Human Atherosclerosis

Dmitry N. Mukhin; Fei-Fei Chao; Howard S. Kruth

From the Institute of Experimental Cardiology, Cardiology Research Center, Russian Academy of Medical Sciences, Moscow, Russia (D.N.M.), and the Section of Experimental Atherosclerosis, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md (F.-F.C., H.S.K.).

Correspondence to Dr Howard S. Kruth, Section of Experimental Atherosclerosis, NHLBI, NIH, Bldg 10, Rm 5N113, 10 Center Dr MSC 1422, Bethesda, MD 20892-1422.

Abstract High accumulation of lipids is a typical feature of an atherosclerotic lesion. We have previously identified the chemical structure of the major glycosphingolipids (GSLs) of human aorta; however, quantification of the absolute concentration of GSLs was not carried out. In the present study, for the first time we have performed a quantitative comparative analysis of GSL composition in the media and two sublayers of the intima taken from normal regions, fatty streaks, and atherosclerotic plaques of the human aorta. The intimal tissue containing fatty streaks and atherosclerotic plaques accumulated GSLs, predominantly glucosylceramide (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 musculoelastic and elastic-hyperplastic intimal layers of normal regions, respectively. We did not observe a significant increase in other GSLs. An increase in the content of gangliosides G_D3 and G_D1a was detected in the media underlying atherosclerotic lesions. On the basis of an analysis of the ratio of GlcCer, LacCer, and G_M3 accumulated in the tissue and cells of the elastic-hyperplastic layer of intima, we have concluded that the accumulation of the above-mentioned GSLs occurs mainly 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 the GSL concentration and distribution within the normal and atherosclerotic 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 of the various GSLs with intimal cells as well as extracellular lipid particles, and (4) metabolic relationships between cholesterol and GSL accumulation.

Key Words: atherosclerosis • aorta • glycosphingolipids • extracellular lipid particles • gangliosides

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