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

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 (SO4)-S-35 incorporation, by 30-50% over that of native LDL, The effect was maximal after 72 h of exposure to 5 mu g/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 (SO4)-S-35 to [H-3]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.