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 (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.
Chang
M Y
MY
Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
Potter-Perigo
S
S
Tsoi
C
C
Chait
A
A
Wight
T N
TN
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000378:metabolism; D001161:Arteriosclerosis / Q000378:metabolism; D002478:Cells, Cultured; D005944:Glucosamine / Q000378:metabolism; D006025:Glycosaminoglycans / Q000737:chemistry / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008254:Macaca nemestrina; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D011509:Proteoglycans / Q000378:metabolism*; D013464:Sulfuric Acids / Q000378:metabolism
D006025:Glycosaminoglycans; D008077:Lipoproteins, LDL; D011509:Proteoglycans; D013464:Sulfuric Acids; C099252:oxidized low density lipoprotein; D005944:Glucosamine