The Effect of Calcitriol on Endothelial Cellular Senescence

Background: Calcitriol, the active hormone of vitamin D₃, affects a wide range of ‘non-classical’ organs and target tissues, including a favorable impact on the cardiovascular system. Cellular senescence is related to phenotypic changes that are implicated in human aging, a process which has been established as a major cardiovascular risk factor. It has been demonstrated that cellular senescence may contribute to the pathogenesis of atherosclerosis, for instance, telomeres are shortened in atherosclerosis-prone areas. The effect of calcitriol on senescence in endothelial cells has not been fully investigated.

Aim: To evaluate the effect of calcitriol on endothelial senescence.

Methods: Human umbilical vein cord endothelial cells (HUVEC) were obtained from umbilical cords and stimulated with hydrogen peroxide (H₂O₂). After stimulation, the cells were treated with calcitriol for 24-48 hours and then harvested. The cells were examined for morphological changes and senescence using beta-Galactosidase staining. Additionally, telomerase activity was measured by a TRAP assay.

Results: H₂O₂ induced morphological changes such as decrease cell number, increase granules and ghost cells. These morphological changes were not observed while adding calcitriol to the stimulated cells. The percentage of cells colored by beta-Galactosidase staining significantly increased due to H₂O₂ stimulation. Treatment with calcitriol decreased beta-Galactosidase staining in stimulated cells (no treatment: 18±2.6%, treatment with H₂O₂: 80±5.3%, treatment with calcitriol and H₂O₂: 11±9%; p<0.05). Telomerase activity was found to be increased in cells treated with calcitriol (calcitriol treatment: 468% vs control: 100%).

Conclusion: The present study demonstrated that calcitriol may decrease stress induced senescence in endothelial cells, at least partly, by increasing the activity of telomerase, which is responsible for telomere lengthening. The effect of calcitriol on stress induced senescence in endothelial cells may be one of the many mechanisms by which calcitriol affect the cardiovascular system.