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Oxidative Medicine and Cellular Longevity
Volume 2018, Article ID 1714896, 13 pages
Research Article

VDR Agonist Prevents Diabetic Endothelial Dysfunction through Inhibition of Prolyl Isomerase-1-Mediated Mitochondrial Oxidative Stress and Inflammation

1The First Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China
2Department of Cardiology, Affiliated Hospital of Putian University, Putian, Fujian, China
3Fujian Provincial Institute of Hypertension, the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China
4Department of Cardiology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China

Correspondence should be addressed to Dajun Chai; moc.621@iahcnujad, Feng Peng; ten.haey@uohzufgnepgnef, and Jinxiu Lin; nc.moc.liamdem@uixnijnil

Meijin Zhang and Liming Lin contributed equally to this work.

Received 24 October 2017; Revised 29 December 2017; Accepted 2 January 2018; Published 15 April 2018

Academic Editor: Eric E. Kelley

Copyright © 2018 Meijin Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background and aim. Upregulation of prolyl isomerase-1 (Pin1) protein expression and activity was associated with the pathogenesis of diabetic vasculopathy through induction of endothelial oxidative stress and inflammation. Moreover, VDR agonist protects against high glucose-induced endothelial apoptosis through the inhibition of oxidative stress. We aimed to explore the effects of the VDR agonist on diabetes-associated endothelial dysfunction and the role of Pin1 in this process. Methods. Streptozocin-induced diabetic mice were randomly treated with vehicle, VDR agonist (10 μg/kg/d, i.g., twice a week), or Pin1 inhibitor, Juglone (1 mg/kg/d, i.p., every other day), for eight weeks. In parallel, human umbilical vein endothelial cells (HUVECs) exposed to high-glucose condition were treated with 1,25-dihydroxyvitamin D3 and Juglone or vehicle for 72 hours. Organ chamber experiments were performed to assess endothelium-dependent relaxation to acetylcholine. Circulatory levels of Pin1, SOD, MDA, IL-1β, IL-6, and NO in diabetic mice, Pin1 protein expression and activity, subcellular distribution of p66Shc, and NF-κB p65 in high glucose-cultured HUVECs were determined. Results. Both VDR agonist and Juglone significantly improved diabetes-associated endothelial dysfunction and reduced high glucose-induced endothelial apoptosis. Mechanistically, the circulatory levels of SOD and NO were increased compared with those of vehicle-treated diabetic mice. Additionally, Pin1 protein expression and activity, p66Shc mitochondrial translocation, and NF-κB p65 in high glucose-cultured HUVECs were also inhibited by VDR agonist and Juglone. Knockdown of VDR abolished the inhibitory effects of VDR agonist on high glucose-induced upregulation of Pin1 protein expression and activity. Conclusions. VDR agonist prevents diabetic endothelial dysfunction through inhibition of Pin1-mediated mitochondrial oxidative stress and inflammation.