The gangliosides of adult human aorta: intima, media and plaque

Abstract

The composition, structure and localization of gangliosides of aorta taken from subjects who had died after myocardial infarction were studied. Individual gangliosides were purified by high-performance liquid chromatography and high-performance thin-layer chromatography and were characterized on the basis of their chromatographic mobility, carbohydrate composition, neuraminidase hydrolysis and methylation analysis. The main aortic gangliosides were identified as GM3, GMI, GD3, GDla and GTlb. Significant differences in the ganglioside composition of intima and media were detected and the ganglioside profile of atherosclerotic plaques was found to differ markedly from that of unaffected intima. The latter was characterized by high content of GD3, a ganglioside thought to be associated with membrane permeability, cell interaction, adhesiveness and growth and to supress unspecific immune responses. Possible implications of the results in low-density lipoprotein binding to the arterial wall and in immunological changes induced by atherosclerotic lesions are discussed.Recently we found that several antigens reacting with monoclonal antibodies raised against aortic cell subpopulations are glycosphingolipids [2]. Earlier it has been shown that there is a threefold increase of gangliosides in the aorta during atherosclerosis [3]. Since gangliosides are important factors determining cell adhesiveness [4] and low-density lipoprotein binding [5] (and the literature cited therein), which both have been suggested to be involved in the development of atherosclerotic lesions (see for example [6]), the ganglioside composition of and localization in human aorta is of considerable interest. Nonetheless, information on this subject is sparse [3, 7, 81. With exeption of GM3 aortic gangliosides were identified only on the basis of their chromatographic mobility and no attempts to differentiate between intimal and medial glycolipids were undertaken. Here we present the results of a detailed study of the gangliosides of adult human aorta, its uninvolved intima, atherosclerotic plaques and underlying media. MATERIALS AND METHODS TissueThe human thoratic aortas from 40 -60-year-old men and women who had died of myocardial infarction were obtained at autopsy within 1.5 -3 h after sudden death. Atherosclerotic lesions (mainly atherosclerotic plaques) occupied, as a rule, about 50% of the total inner surface of the aorta. Adventitia together with one third of the outer media were stripped away and the remaining parts of aortic material were washed and frozen until analysis. The grossly normal areas and the unCorrespondence to N. V. Prokazova, Institut Cardiologii Akademii Meditsinskikh Nauk SSSR, 3 Cherepkovskaya ulitsa 15A, Moskva, USSR 121552Abbreviations. The designation of gangliosides follows the IUPAC-IUB recommendations [l]: GM3, I13NeuAcLacCer; Ghll, I13NeuAcGgOse4Cer; GD3, I13(NeuAc)2LacCer; GD1,, I13,1V3-(Ne~Ac)~GgOse~Cer; GTl I13(Ne~A~)ZIV3NeuAcGgOse4Cer. complicated atherosclerotic plaques were cut out and inner intima consistin...

Monoclonal antibody B2, a marker of neuroendocrine sympathoadrenal precursors, recognizes the Luke (LKE) antigen

“…After filtration, both lipid extracts were pooled, dried in vacuo, and then resuspended in 0.5 mol per L methanolic sodium hydroxide. After incubation at 37°C for 5 hours to saponify the bulk of alkali‐labile phospholipids, 33 samples were dried and dialyzed against distilled water (MW cutoff, 3000; Spectra‐Por, Houston, TX; 4°C) to desalt samples. After being dried, samples were resuspended in 100 mL C‐M‐water (30:60:8, vol/vol/vol) and applied to a DEAE‐A25 Sephadex column (10 mL bed volume [BV], Sigma Chemical Co.).…”

Gangliosides in normal human serum

“…The origin, fate and biological function of endogenous serum glycosphingolipids, both neutral and acid are still not known. A recent report on the altered ganglioside content in atherosclerotic human aorta [34] points to the possibility that the disordered metabolism of lipoprotein-bound glycosphingolipids in serum could play a role in the pathogenesis of atherosclerosis in man.…”

Isolation and structural characterization of glycosphingolipids of in vitro propagated bovine aortic endothelial cells

“…This indicated the existence of mechanisms which can produce different degrees of polarity for specific lipids in polarized epithelial cells. Al-though the importance of GSLs as cell surface antigens and receptors has received increasing attention in recent years, spare information is available about GSLs of cultured bovine (Kanda et al, 1994) and human endothelial cells (Gillard et al, 1987(Gillard et al, , 1991, and of intima cells from normal and atherosclerotic human aorta (Prokazova et al, 1987(Prokazova et al, , 1989; for review, see Bergelson, 1995).…”