Accumulation of glycosphingolipids in human atherosclerotic plaque and unaffected aorta tissues.
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 GlcCer data was expressed as (micrograms GlcCer/mg cholesterol and/mg total phospholipid, a 28-fold and 7-fold 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 UDP-GlcCer: ceramide beta 1-->4 glucosyltransferase (GlcT-1) was similar in unaffected tissue, fatty streaks, and plaques. However, the activity of UDP-galactose: GlcCer, beta 1-->4 galactosyltransferase (GalT-2) activity was moderately higher in plaque than in unaffected tissue. LacCer, but not GlcCer derived from plaque intima exerted a approximately 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.
Chatterjee
S B
SB
Department of Pediatrics, Johns Hopkins University, School of Medicine, Baltimore, MD 21287-3654, USA.
Dey
S
S
Shi
W Y
WY
Thomas
K
K
Hutchins
G M
GM
D000328:Adult; D000368:Aged; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001161:Arteriosclerosis / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D001792:Blood Platelets / Q000378:metabolism; D002114:Calcinosis; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D005227:Fatty Acids / Q000097:blood; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006026:Glycoside Hydrolases / Q000378:metabolism; D006028:Glycosphingolipids / Q000097:blood / Q000378:metabolism*; D016695:Glycosyltransferases / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism
D005227:Fatty Acids; D006028:Glycosphingolipids; D008077:Lipoproteins, LDL; D010743:Phospholipids; C099252:oxidized low density lipoprotein; D002784:Cholesterol; D016695:Glycosyltransferases; D006026:Glycoside Hydrolases