Endothelial pro-atherosclerotic response to extracellular diabetic-like environment: Possible role of thioredoxin-interacting protein

Tali Zitman-Gal*, Janice Green, Metsada Pasmanik-Chor, Varda Oron-Karni, Jacques Bernheim

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background. High blood and tissue concentrations of glucose and advanced glycation end-products (AGEs) are thought to play an important role in the development of vascular diabetic complications. Therefore, the impact of extracellular AGEs and different glucose concentrations was evaluated by studying the gene expressions and the underlying cellular pathways involved in the development of inflammatory pro-atherosclerotic processes observed in cultured endothelial cells.Methods. Fresh human umbilical vein cord endothelial cells (HUVEC) were treated in the presence of elevated extracellular glucose concentrations (5.5-28 mmol/l) with and without AGE-human serum albumin (HSA). Affymetrix GeneChip® Human Gene 1.0 ST arrays were used for gene expression analysis (total 20 chips). Genes of interest were further validated using real-time PCR and western blot techniques.Results. Microarray analysis revealed significant changes in some gene expressions in the presence of the different stimuli, suggesting that different pathways are involved. Six genes were selected for validation as follows: thioredoxin-interacting protein (TXNIP), thioredoxin (TXN), nuclear factor of kappa B (NF-κB), interleukin 6 (IL6), interleukin 8 (IL8) and receptor of advanced glycation end-products (RAGE). Interestingly, it was found that the association of AGEs together with the highest pathophysiological concentration of glucose (28 mmol/l) diminished the expression of these specific genes, excluding TXN.Conclusions. In the present model that mimics a diabetic environment, the relatively short-term experimental conditions used showed an unexpected blunting action of AGEs in the presence of the highest glucose concentration (28 mmol/l). The interactive cellular pathways involved in these processes should be further investigated.

Original languageEnglish
Pages (from-to)2141-2149
Number of pages9
JournalNephrology Dialysis Transplantation
Issue number7
StatePublished - Jul 2010


FundersFunder number
Isaac Katzenelen-bogen Dermatology Research Fund
Meir Medical Center Israel
Pearl Klayman Cathedra of Urology
Sackler Faculty of Medicine, Tel Aviv University


    • advanced glycation end-products
    • diabetes
    • endothelial cells
    • thioredoxin-interacting protein


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