Calcitriol blunts the deleterious impact of advanced glycation end products on endothelial cells

摘要

Calcitriol blunts the deleterious impact of advanced glycation end products on endothelial cells. Am J Physiol Renal Physiol 294: F1059-F1064, 2008. First published March 19, 2008; doi: 10.1152/ajprenal.00051.2008.-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-kB 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-KB-p65 DNA binding activity was enhanced and associated with a decrease in inhibitor kB