Abstract
Aim:
To explore the protective effects and related mech-anisms of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) on en-dothelial 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)2D3, 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 proinflam-matory cytokines. 1,25(OH)2D3 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)2D3 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)2D3.
Conclusions:
1,25(OH)2D3 attenuates high-glucose-induced endothelial oxidative injury through upregulation of the Nrf2 antioxidant pathway in a VDR-dependent manner.
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