Glycobiology vol 7 no 1 pp. 57-65, 1997
© 1997
research-article |
Accumulation of glycosphingolipids in human atherosclerotic plaque and unaffected aorta tissues
Department of Pediatrics, Lipid Research Arteriosclerosis Unit Baltimore, MD 21287-3654, USA
1Department of Pathology, The Johns Hopkins University, School of Medicine Baltimore, MD 21287-3654, USA
2To whom correspondence should be addressed at CMSC 604, The Johns Hopkins Hospital, Baltimore, MD 21287-3654, USA
Received on June 6, 1996; revised on July 5, 1996; accepted on July 11, 1996
We have measured the levels of glycosphingolipids and the activity of glycosphingolipid glycosyltransferases in human aortic intima and media from patients who died of atherosclerosis. The effects of lactosylceramide (LacCer) and glucosylceramide (GlcCer) from plaque intima on smooth muscle cell proliferation were assessed. When the GIcCer data was expressed as (pg GlcCer/mg cholesterol and/mg total phospholipid, a 28-fold and 7-told increase in plaque intima compared to normal intima was observed. Similarly, the level of LacCer was elevated 5-fold and 4-fold, respectively, compared to unaffected intima. The activity of UDPGicCer: ceramide ß1
4 glucosyltransferase (GlcT-1) was similar in unaffected tissue, fatty streaks, and plaques. However, the activity of UDP-galactose: GlcCer, ß1
4 galactosyltransferase (GalT-2) activity was moderately higher in plaque than in unaffected tissue. LacCer, but not GlcCer derived from plaque intima exerted a -2.8-fold increase in the proliferation of human aortic smooth muscle cells grown in tissue culture compared to control presumably due to a marked increase in LacCer molecular species containing C16:0, C22:1, and C24:0 fatty acids in plaque intima compared to control. In sum, our findings provide an interesting and novel pathogenic mechanism of lactosylceramide mediated plaque formation via stimulation of aortic smooth muscle cell proliferation.
cell proliferation
GlcCer ß14 galactosyltransferase (GalT-2)
lactosylceramide (LacCer)
oxidized low density lipoprotein (Ox-LDL)
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