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

@article{citeulike:2744904, 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-{kappa}B 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-{kappa}B-p65 DNA binding activity was enhanced and associated with a decrease in inhibitor {kappa}B{alpha} (I{kappa}B{alpha}) and an increase in phosphorylated (p)-I{kappa}B{alpha} levels. Addition of calcitriol blunted the AGEs-induced elevation of NF-{kappa}B-p65 DNA binding activity, a phenomenon related to an increased expression of I{kappa}B{alpha}. This increase was correlated to declined p-I{kappa}B{alpha} 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. 10.1152/ajprenal.00051.2008}, author = {Talmor, Yeela and Golan, Eliezer and Benchetrit, Sydney and Bernheim, Jacques and Klein, Osnat and Green, Janice and Rashid, Gloria }, citeulike-article-id = {2744904}, doi = {10.1152/ajprenal.00051.2008}, journal = {Am J Physiol Renal Physiol}, keywords = {age, cv, vitamin-d}, month = {May}, number = {5}, pages = {F1059--1064}, posted-at = {2008-05-02 11:13:38}, priority = {2}, title = {Calcitriol blunts the deleterious impact of advanced glycation end products on endothelial cells}, url = {http://dx.doi.org/10.1152/ajprenal.00051.2008}, volume = {294}, year = {2008} }

TY - JOUR ID - citeulike:2744904 L3 - citeulike-article-id:2744904 TI - Calcitriol blunts the deleterious impact of advanced glycation end products on endothelial cells JF - Am J Physiol Renal Physiol VL - 294 IS - 5 SP - F1059 EP - 1064 N2 - 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-{kappa}B 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-{kappa}B-p65 DNA binding activity was enhanced and associated with a decrease in inhibitor {kappa}B{alpha} (I{kappa}B{alpha}) and an increase in phosphorylated (p)-I{kappa}B{alpha} levels. Addition of calcitriol blunted the AGEs-induced elevation of NF-{kappa}B-p65 DNA binding activity, a phenomenon related to an increased expression of I{kappa}B{alpha}. This increase was correlated to declined p-I{kappa}B{alpha} 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. 10.1152/ajprenal.00051.2008 KW - age KW - cv KW - vitamin-d AU - Talmor, Yeela AU - Golan, Eliezer AU - Benchetrit, Sydney AU - Bernheim, Jacques AU - Klein, Osnat AU - Green, Janice AU - Rashid, Gloria PY - 2008/05/01/ UR - http://dx.doi.org/10.1152/ajprenal.00051.2008 ER -