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 proces ses 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 ex hibit altered lipoprotein binding properties. Ox-LDL stimulated glycosamino glycan synthesis, as measured by (SO4)-S-35 incorporation, by 30-50% over t hat 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 increa sed in response to Ox-LDL, as indicated by size exclusion chromatography an d SDS-polyacrylamide gel electrophoresis. These effects could be mimicked b y the lipid extract of Ox-LDL, These size increases were largely due to cha in elongation and not to alterations in the ratio of (SO4)-S-35 to [H-3]glu cosamine incorporation. Affinity chromatography indicated that Ox-LDL stimu lated the synthesis of proteoglycans with high affinity for native LDL, Ox- LDL also specifically stimulated mRNA expression for biglycan (but not vers ican or decorin), which was correlated with increased expression of secrete d biglycan, Thus, Ox-LDL may influence lipoprotein retention by regulating synthesis of biglycan and also by altering glycosaminoglycan synthesis of v ascular proteoglycans so as to enhance lipoprotein binding properties.