Abstract
Aims/hypothesis. Retention of atherogenic lipoproteins in the artery wall by proteoglycans is a key step in the development of atherosclerosis. Thiazolidinediones have been shown to reduce atherosclerosis in mouse models. The aim of this study was to determine whether thiazolidinediones modify vascular proteoglycan synthesis in a way that decreases LDL binding. Methods. Primate aortic smooth muscle cells were exposed to troglitazone or rosiglitazone, or no stimulus at all for a 24-hour steady-state labelling period. Sulphate incorporation, size and LDL binding affinity of proteoglycans were determined. Proteoglycans secreted by cells in the presence or absence of troglitazone were separated into large and small classes by size exclusion chromatography, and LDL binding affinity was determined. Results. Proteoglycans synthesised by cells exposed to troglitazone or rosiglitazone were smaller, with decreased sulphate incorporation and decreased LDL binding affinity. However, troglitazone had a greater effect than rosiglitazone. Troglitazone reduced the LDL binding affinities of both the large and small proteoglycans compared with control. The binding differences persisted when glycosaminoglycan chains released from proteoglycans were incubated with LDL, indicating that troglitazone affects the glycosaminoglycan synthetic machinery of these cells. Conclusions/interpretation. Thiazolidinediones decrease the LDL binding affinity of the proteoglycans synthesised by primate aortic smooth muscle cells. This could, in part, account for the reduced atherosclerosis observed in animal models.
Original language | English |
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Pages (from-to) | 837-843 |
Number of pages | 7 |
Journal | Diabetologia |
Volume | 47 |
Issue number | 5 |
DOIs | |
State | Published - May 2004 |
Bibliographical note
Funding Information:Acknowledgements. This work was supported in part by Na-
Funding
Acknowledgements. This work was supported in part by Na-
Funders | Funder number |
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National Institutes of Health (NIH) | HL18645, DK02456, AT00555, RR12609 |
National Institute of Diabetes and Digestive and Kidney Diseases | P30DK035816 |
Diabetes Australia Research Trust | |
National Heart Foundation of Australia |
Keywords
- Atherosclerosis
- Glycosaminoglycans
- Lipoprotein retention
- Proteoglycans
- Rosiglitazone
- Thiazolidinediones
- Troglitazone
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism