Susceptibility of VLDL subfractions to oxidation in patients with tyep2 diabetes mellitus and their effect on vascular cell adhesion molecules expression in endothelial cells

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Hyperalphalipoproteinaemia in Chinese is associated with a reduction in cholesteryl ester transfer protein activity

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Cholesteryl ester transfer protein gene polymorphisms in Chinese patients with non-insulin-dependent diabetes mellitus

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Correlation between plasma phospholipid transfer protein activity and low density lipoprotein subfractions pattern in subjects with type 2 diabetes mellitus

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Association between serum concentrations of soluble lectin-like oxidized low density lipoprotein receptor-1 and serum amyloid A in type 2 diabetes

This journal suppl. entitled: Abstracts of the 10th International Diabetes Federation-Western Pacific Region Congress and the 6th AASD Scientific MeetingPosters: no. PO020BACKGROUND: Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) mediates the uptake of oxidized LDL in endothelial cells and macrophages, and has been implicated in the pathogenesis of vascular inflammation and atherosclerosis. The extracellular domain of LOX-1 can be proteolytically cleaved and released as a soluble form (sLOX-1). It has been suggested that circulating level of sLOX-1 reflects LOX-1 expression and can act as a biomarker. LOX-1 expression is inducible and recent experimental data have shown that serum amyloid A (SAA), an acute phase protein, can induce LOX-1 expression in macrophages in vitro. Since type 2 diabetes is associated with subclinical inflammation, we have evaluated whether serum sLOX-1 level is ...postprin

Upregulation of lectin-like oxidized LDL receptor by advanced glycation end products in endothelial cells

Poster Session 3 – Diabetes, Insulin Resistance and Atherosclerosis: Poster no. 323 - Wednesday abstract no. 637OBJECTIVE: Lectin-like oxidized LDL receptor-1 (LOX-1) is a class E oxidized LDL specific scavenger receptor and LOX-1 expression is inducible. LOX-1 has been implicated in atherogenesis and LOX-1 expression is increased in diabetes. It has been suggested that advanced glycation end products (AGE) may contribute to the induction of LOX-1 in diabetes and we have investigated the ...postprintThe 16th International Symposium on Atherosclerosis (ISA2012), Sydney, Australia, 25-29 March 2012

Serum Level of Soluble Receptor for Advanced Glycation End Products Is Associated with A Disintegrin And Metalloproteinase 10 in Type 1 Diabetes

Background The receptor for advanced glycation end products (RAGE) is involved in the pathogenesis of diabetic complications, and soluble forms of the receptor (sRAGE) can counteract the detrimental action of the full-length receptor by acting as decoy. Soluble RAGE is produced by alternative splicing [endogenous secretory RAGE (esRAGE)] and/or by proteolytic cleavage of the membrane-bound receptor. We have investigated the role of A Disintegrin And Metalloproteinase 10 (ADAM10) in the ectodomain shedding of RAGE. Methods Constitutive and insulin-induced shedding of RAGE in THP-1 macrophages by ADAM10 was evaluated using an ADAM10-specific metalloproteinase inhibitor. Serum ADAM10 level was measured in type 1 diabetes and control subjects, and the association with serum soluble RAGE was determined. Serum total sRAGE and esRAGE were assayed by ELISA and the difference between total sRAGE and esRAGE gave an estimated measure of soluble RAGE formed by cleavage (cRAGE). Results RAGE shedding (constitutive and insulin-induced) was significantly reduced after inhibition of ADAM10 in macrophages, and insulin stimulated ADAM10 expression and activity. Diabetic subjects have higher serum total sRAGE and esRAGE (p<0.01) than controls, and serum ADAM10 was also increased (p<0.01). Serum ADAM10 correlated with serum cRAGE in type 1 diabetes (r = 0.40, p<0.01) and in controls (r = 0.31. p<0.01) but no correlations were seen with esRAGE. The association remained significant after adjusting for age, gender, BMI, smoking status and HbA1c. Conclusion Our data suggested that ADAM10 contributed to the shedding of RAGE. Serum ADAM10 level was increased in type 1 diabetes and was a significant determinant of circulating cRAGE.published_or_final_versio

Cellular cholesterol transport proteins in diabetic nephropathy

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Effects of advanced glycation end products on caveolin-1 and endothelial nitric oxide synthase in endothelial cells

Objective: Recent studies have suggested that advanced glycation end products (AGEs) may be one of the causes of endothelial dysfunction in diabetes mellitus. However, the underlying mechanism(s) are not fully understood. Since AGEs bind to the receptor for advanced glycation end products (RAGE) in caveolae, this study was performed to investigate whether AGEs influence endothelial nitric oxide synthase (eNOS) activity by affecting caveolin-1 which is involved in the post-translational regulation of eNOS. Methods: Caveolin-1 enriched membrane fractions were isolated from human aortic endothelial cells using a modified detergent-free extraction procedure. Isolated caveolae were subjected to Western blotting analyses with anti-caveolin-1, eNOS and RAGE antibodies. Nitric oxide (NO) production in response to AGEs was measured by colorimetric assay. Results: AGEs reduced NO production by endothelial cells in a dose-dependent manner despite no significant change in eNOS mRNA and protein in total cell lysate. Treatment with 200 mg/mL AGEs significantly increased protein levels of caveolin-1 (24.4%±3.7 vs. 13.5±5.6 in untreated control, p=0.03) and RAGE (30.0%±6.9 vs. 12.6±2.1, p=0.04) in caveolae compartment which was associated with a reduction in eNOS activity and NO production. This resulted in increased expression of adhesion molecules like vascular cell adhesion molecule-1 in the endothelial cells. Conclusion: Our results suggest that AGEs induce endothelial dysfunction by increasing caveolin-1 expression in endothelial cells and reduce eNOS activity and NO production. Whether the upregulation of caveolin-1 is mediated by the interaction of AGEs with RAGE warrants further investigations