Abstract
Aim: To explore the protective effects and related mechanisms of 1,25 dihydroxyvitamin D<sub>3</sub> (1,25(OH)<sub>2</sub>D<sub>3</sub>) on endothelial dysfunction under hyperglycemic conditions. Methods: Cultured human umbilical vein endothelial cells (HUVECs) were treated with normal glucose (glucose concentration of 5.5 mmol/L), high glucose (glucose concentration of 33 mmol/L), and high glucose plus 1,25(OH)<sub>2</sub>D<sub>3</sub>, respectively. Cell viability and apoptosis, intracellular reactive oxygen species (ROS) and nitric oxide (NO) contents, antioxidant enzyme activities, proinflammatory cytokine mRNA levels, and expression levels of proteins involved were measured. Results: High glucose decreased HUVEC viability, promoted ROS production and apoptosis, and reduced NO generation, which was associated with decreased activities of antioxidant enzymes and increased levels of proinflammatory cytokines. 1,25(OH)<sub>2</sub>D<sub>3</sub> treatment enhanced HUVEC viability, attenuated ROS generation and apoptosis, and increased NO production, which was accompanied by enhanced antioxidant enzyme activities and reduced proinflammatory factors. Mechanically, 1,25(OH)<sub>2</sub>D<sub>3</sub> promoted nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) in a vitamin D receptor (VDR)-dependent manner, and Nrf2 siRNA abolished the antioxidative and anti-inflammatory effects of 1,25(OH)<sub>2</sub>D<sub>3</sub>. Conclusions: 1,25(OH)<sub>2</sub>D<sub>3</sub> attenuates high-glucose-induced endothelial oxidative injury through upregulation of the Nrf2 antioxidant pathway in a VDR-dependent manner.
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