title: Calcitriol blunts the deleterious impact of advanced glycation end products on endothelial cells.
abstract: Advanced glycation end products (AGEs), which are elevated in diabetic and uremic patients, may induce vascular dysfunctions, and calcitriol may improve the cardiovascular complications. Therefore, we examined whether calcitriol may modify the endothelial response to AGEs stimulation. Knowing the importance of nuclear factor-kappaB in endothelial inflammatory responses, the effect of AGEs and calcitriol on this pathway was also studied. Calcitriol was added to endothelial cells previously incubated with AGE-human serum albumin (HSA). AGE-HSA induced a decrease in endothelial nitric oxide synthase (eNOS) mRNA expression and enzyme activity. Addition of calcitriol to AGE-HSA-treated endothelial cells improved the decreased action of AGEs on the eNOS system. AGE-HSA increased the AGEs receptor mRNA and protein, which were both blunted by calcitriol. The parallel elevation of interleukin-6 mRNA in the presence of AGE-HSA was also blunted by calcitriol. The NF-kappaB-p65 DNA binding activity was enhanced and associated with a decrease in inhibitor kappaBalpha (IkappaBalpha) and an increase in phosphorylated (p)-IkappaBalpha levels. Addition of calcitriol blunted the AGEs-induced elevation of NF-kappaB-p65 DNA binding activity, a phenomenon related to an increased expression of IkappaBalpha. This increase was correlated to declined p-IkappaBalpha levels. The present results support the concept that calcitriol may act as a vascular protective agent counteracting the probable deleterious actions of AGEs on endothelial cell activities.
authors: Renal Physiology Laboratory, Department of Nephrology and Hypertension, Meir Medical Center, Kfar-Saba, Tchernichovsky 59, Kfar-Saba 44281, Israel.
authors: Yeela
authors: Y
authors: Talmor
authors: Eliezer
authors: E
authors: Golan
authors: Sydney
authors: S
authors: Benchetrit
authors: Jacques
authors: J
authors: Bernheim
authors: Osnat
authors: O
authors: Klein
authors: Janice
authors: J
authors: Green
authors: Gloria
authors: G
authors: Rashid
mesh_terms: D015153:Blotting, Western; D002117:Calcitriol / Q000494:pharmacology*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012710:Serum Albumin, Bovine / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002120:Calcium Channel Agonists; D017127:Glycation End Products, Advanced; D015850:Interleukin-6; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D012710:Serum Albumin, Bovine; D012313:RNA; D052250:Nitric Oxide Synthase Type III; D002117:Calcitriol