Cellular senescence determines endothelial cell damage induced by uremia

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• 作者：Julia Carracedo ; Paula Buend¨ªa ; Ana Merino ; Sagrario Soriano ; Elvira Esquivias ; Alej ; ro Mart¨ªn-Malo ; Pedro Aljama ; Rafael Ram¨ªrez
• 关键词：HUVEC ; human umbilical vein endothelial cells ; ROS ; reactive oxygen species ; CVD ; cardiovascular disease ; SIPS ; stress-induced premature senescence ; CKD ; chronic kidney disease ; MDR-D ; modification of diet in renal disease ; ClCr ; creatinine clearance ; PDs
• 刊名：Experimental Gerontology
• 出版年：2013
• 出版时间：August, 2013
• 年：2013
• 卷：48
• 期：8
• 页码：766-773
• 全文大小：1054 K

文摘

Renal dysfunction is closely associated with endothelial damage leading to cardiovascular disease. However, the extent to which endothelial damage induced by uremia is modulated by aging is poorly known. Aging can render endothelial cells more susceptible to apoptosis through an oxidative stress-dependent pathway. We examined whether senescence-associated to oxidative stress determines the injury induced by the uremia in endothelial cells.

Human umbilical vein endothelial cells (HUVEC) was incubated with human uremic serum and, in the animal model, endothelial cells were obtained from aortas of uremic and no uremic rats. Vitamin C was used to prevent oxidative stress. Senescence, assessed by telomere length and enzyme-betagalactosidase (¦Â-gal), reactive oxygen species (ROS), mitochondrial depolarization (JC-1 probe), caspase 3, and apoptosis were determined by flow cytometry. NF-¦ÊB activity was determined by Western blot.

Uremic serum increased ROS and NF-¦ÊB in young and aging HUVEC. However only in aging cells, uremic serum induced apoptosis (vs young HUVEC, p < 0.01). The endothelial damage induced by uremia seems to be related with the increased oxidative stress, since in both HUVEC and in the experimental model of renal disease in rats, vitamin C prevents endothelial apoptosis. However, vitamin C did not decrease the oxidative stress associated to senescence. These results showed that as compared with young cells, senescent cells have high sensitivity to damage associated to the oxidative stress induced by the uremia. Consequently, protecting senescent endothelial cells from increased oxidative stress might be an effective therapeutic approach in the treatment of vascular disorders in chronic kidney diseases.