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.
Highlights
Ification of these retained lipoproteins by processes such as oxidation [8]
The effects of Oxidized low density lipoproteins (LDL) (Ox-LDL) on chain length of the individual components of Peak 2 could not be resolved by this method, these results suggest that the Ox-LDL effect of glycosaminoglycan chain elongation is not selective for specific proteoglycan molecules but rather applies to all of the major proteoglycans secreted by smooth muscle cell (SMC)
Ox-LDLs have been found to have a variety of biological effects that may be important to atherogenesis (49 –51)
Summary
Ification of these retained lipoproteins by processes such as oxidation [8]. little is known about whether and how oxidative processes might influence lipoprotein retention within the arterial wall. Ox-LDL Stimulates 35SO4 Incorporation into Proteoglycans—To characterize the effects of N-LDL and Ox-LDL on [35SO4]proteoglycan synthesis, SMC treated for up to 72 h with 0 –25 g/ml N-LDL or Ox-LDL were metabolically labeled with 35SO4 for the 6 h time period following lipoprotein treatment. By SDS-PAGE, Ox-LDL increased the apparent molecular size of both bands 3 and 4, as compared with the size of these molecules secreted from control or N-LDL-treated cells (Fig. 2A).
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