title: Marked alteration of proteoglycan metabolism in cholesterol-enriched human arterial smooth muscle cells.
abstract: To elucidate the correlation between vascular cholesterol metabolism and proteoglycan (PrGl) biosynthesis, we investigated PrGl synthesis in human aortic smooth muscle cells (SMCs) after cholesterol enrichment with cationized low-density lipoproteins (LDL). Compared with normal SMCs, total PrGl synthesis by cholesterol-enriched cells decreased 2.4-fold (11874 +/- 530 d.p.m. per 10(5) cells compared with 4890 +/- 385 d.p.m. per 10(5) cells). This was the net result of a 6.9-fold reduction in medium PrGl (11000 +/- 490 d.p.m. per 10(5) cells compared with 1580 +/- 246 d.p.m. per 10(5) cells) and a 3.8-fold increase in cellular PrGl over controls (874 +/- 27 d.p.m. per 10(5) cells compared with 3310 +/- 193 d.p.m. per 10(5) cells). Prior incubation of SMCs with native LDL had no effect on PrGl synthesis by these cells. The decrease in PrGl synthesis in cholesterol-enriched cells correlated with a 90% and 20% reduction in the steady-state level of mRNA for biglycan and decorin respectively, and a virtual elimination of the steady-state level of mRNA for versican over controls. Despite the down-regulation of PrGl synthesis, cholesterol-loaded cells produced a 2-fold increase in a PrGl subfraction with high affinity for LDL. Compared with the corresponding PrGl subfraction from normal cells, that from the cholesterol-enriched cells exhibited increased charge density and a higher molecular mass and contained relatively larger proportions of chondroitin 6-sulphate and dermatan sulphate. These results show that PrGl metabolism is dramatically altered in cholesterol-enriched human SMCs.
authors.affiliation: Section of Cardiology, Louisiana State University Medical Center, New Orleans 70112, USA.
authors.forename: P
authors.initials: P
authors.lastname: Vijayagopal
authors.forename: J E
authors.initials: JE
authors.lastname: Figueroa
authors.forename: Q
authors.initials: Q
authors.lastname: Guo
authors.forename: J D
authors.initials: JD
authors.lastname: Fontenot
authors.forename: Z
authors.initials: Z
authors.lastname: Tao
mesh_terms: D058578:Biglycan; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism; D002846:Chromatography, Affinity; D058575:Decorin; D016326:Extracellular Matrix Proteins; D006801:Humans; D037181:Lectins, C-Type; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011509:Proteoglycans / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053675:Versicans
chemical_list: C546884:BGN protein, human; D058578:Biglycan; D011508:Chondroitin Sulfate Proteoglycans; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D008077:Lipoproteins, LDL; D011509:Proteoglycans; D012333:RNA, Messenger; C508322:VCAN protein, human; D053675:Versicans; D002784:Cholesterol