Thiazolidinediones reduce the LDL binding affinity of non-human primate vascular cell proteoglycans

L.R. Tannock, P.J. Little, Hugh Tsoi, T.N. Wight, A. Chait

    Research output: Contribution to journalArticle

    23 Citations (Scopus)

    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 languageEnglish
    Pages (from-to)837-843
    JournalDiabetologia
    Volume47
    Issue number5
    DOIs
    Publication statusPublished - 2004

    Fingerprint

    Dive into the research topics of 'Thiazolidinediones reduce the LDL binding affinity of non-human primate vascular cell proteoglycans'. Together they form a unique fingerprint.

    Cite this