Oxidized low density lipoproteins regulate synthesis of monkey aortic smooth muscle cell proteoglycans that have enhanced native low density lipoprotein binding properties

J Biol Chem. 2000 Feb 18;275(7):4766-73. doi: 10.1074/jbc.275.7.4766.

Abstract

Oxidized low density lipoproteins (Ox-LDL) affect several biological processes involved in atherogenesis. However, it is not known whether Ox-LDL can regulate proteoglycan expression and thus affect arterial wall lipoprotein retention. This study evaluated whether Ox-LDL, as compared with native LDL, regulates proteoglycan expression by monkey arterial smooth muscle cells in vitro and whether proteoglycans synthesized in the presence of Ox-LDL exhibit altered lipoprotein binding properties. Ox-LDL stimulated glycosaminoglycan synthesis, as measured by (35)SO(4) incorporation, by 30-50% over that of native LDL. The effect was maximal after 72 h of exposure to 5 microg/ml of Ox-LDL. The molecular sizes of versican, biglycan, and decorin increased in response to Ox-LDL, as indicated by size exclusion chromatography and SDS-polyacrylamide gel electrophoresis. These effects could be mimicked by the lipid extract of Ox-LDL. These size increases were largely due to chain elongation and not to alterations in the ratio of (35)SO(4) to [(3)H]glucosamine incorporation. Affinity chromatography indicated that Ox-LDL stimulated the synthesis of proteoglycans with high affinity for native LDL. Ox-LDL also specifically stimulated mRNA expression for biglycan (but not versican or decorin), which was correlated with increased expression of secreted biglycan. Thus, Ox-LDL may influence lipoprotein retention by regulating synthesis of biglycan and also by altering glycosaminoglycan synthesis of vascular proteoglycans so as to enhance lipoprotein binding properties.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aorta, Thoracic / cytology
  • Aorta, Thoracic / metabolism
  • Arteriosclerosis / metabolism
  • Cells, Cultured
  • Glucosamine / metabolism
  • Glycosaminoglycans / chemistry
  • Glycosaminoglycans / metabolism
  • Lipoproteins, LDL / metabolism*
  • Macaca nemestrina
  • Muscle, Smooth / cytology
  • Muscle, Smooth / metabolism*
  • Protein Binding
  • Proteoglycans / metabolism*
  • Sulfuric Acids / metabolism

Substances

  • Glycosaminoglycans
  • Lipoproteins, LDL
  • Proteoglycans
  • Sulfuric Acids
  • oxidized low density lipoprotein
  • Glucosamine