ArticleDiabetologia2004
Fenofibrate modifies human vascular smooth muscle proteoglycans and reduces lipoprotein binding.
Article in Diabetologia, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 29 citations in OpenAlex.
- Multiple Growth Factors, But Not VEGF, Stimulate Glycosaminoglycan Hyperelongation in Retinal Choroidal Endothelial Cells.International journal of biological sciences · 2016Article
- Proteoglycan mediated lipoprotein retention: a mechanism of diabetic atherosclerosis.Reviews in endocrine & metabolic disorders · 2008Review
- Biosynthesis of natural and hyperelongated chondroitin sulfate glycosaminoglycans: new insights into an elusive process.The open biochemistry journal · 2008Article
- Vascular wall proteoglycan synthesis and structure as a target for the prevention of atherosclerosis.Vascular health and risk management · 2007Review
- Actions of calcium channel blockers on vascular proteoglycan synthesis: relationship to atherosclerosis.Vascular health and risk management · 2005Review
- Smad2-dependent glycosaminoglycan elongation in aortic valve interstitial cells enhances binding of LDL to proteoglycans.Cardiovascular pathology : the official journal of the Society for Cardiovascular PathologyArticle
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Authors and funding
6 authors at 5 institutions in 1 country.
Funding
Abstract
aims/hypothesisVascular disease in type 2 diabetes is associated with an up-regulation of atherogenic growth factors, which stimulate matrix synthesis including proteoglycans. We have examined the direct actions of fenofibrate on human vascular smooth muscle cells (VSMCs) and have specifically investigated proteoglycan synthesis and binding to LDL.
methodsProteoglycans synthesised by human VSMCs treated with fenofibrate (30 micromol/l) were assessed for binding to human LDL using a gel mobility shift assay, metabolically labelled with [(35)S]-sulphate and quantitated by cetylpyridinium chloride. They were then assessed for electrophoretic mobility by SDS-PAGE, for size by gel filtration, for sulphation pattern by fluorophore-assisted carbohydrate electrophoresis, and for glycosaminoglycan (GAG) composition by enzyme digestion.
resultsProteoglycans synthesised in the presence of fenofibrate showed an increase in the half-maximum saturation concentration of LDL from 36.8+/-12.4 microg/ml to 77.7+/-17 microg/ml under basal conditions, from 24.9+/-4.6 microg/ml to 39.1+/-6.1 microg/ml in the presence of TGF-beta1, and from 9.5+/-4.4 microg/ml to 31.1+/-3.4 microg/ml in the presence of platelet-derived growth factor/insulin. Fenofibrate treatment in the presence of TGF-beta1 inhibited the incorporation of [(35)S]-sulphate into secreted and cell-associated proteoglycans synthesised by human VSMCs by 59.2% (p<0.01) and 39.8% (p<0.01) respectively. The changes in sulphate incorporation following treatment with fenofibrate were associated with a concentration-related increase in the electrophoretic mobility due to a reduction in GAG length. There was no change in the sulphation pattern; however, there was an alteration in the disaccharide composition of the GAGs. CONCLUSIONS/
interpretationFenofibrate modifies the structure of vascular proteoglycans by reducing the length of the GAG chains and GAG composition, resulting in reduced binding to human LDL, a mechanism which may lead to a reduction of atherosclerosis and cardiovascular disease in people with diabetes treated with fenofibrate.
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