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22 December 2016 Vitamin D suppresses oxidative stress-induced microparticle release by human umbilical vein endothelial cells
Xiuyue Jia, Jie Xu, Yang Gu, Xin Gu, Weimin Li, Yuping Wang
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Abstract

Endothelial microparticle (MP) release was increased in numerous cardiovascular diseases including preeclampsia. Oxidative stress is a potent inducer of endothelial dysfunction. In this study, we aimed to investigate if vitamin D could protect endothelial cells (ECs) from MP release induced by oxidative stress. Endothelial cell (from human umbilical vein) oxidative stress was induced by cultivation of cells under lowered oxygen condition (2%O2) for 48 h and cells cultured under standard condition (21%O2) served as control. 1,25(OH)2D3 was used as bioactive vitamin D. Using annexin-V as a marker of released MP assessed by flow cytometry and cytochrome c reduction assay to measure EC superoxide generation, we found that MP release and superoxide generation were significantly increased when cells were cultured under 2%O2, which could be significantly inhibited by 1,25(OH)2D3. To study the potential mechanisms of 1,25(OH)2D3 protective effects on ECs, EC expression of endothelial nitric oxide synthase (eNOS), p-eNOSSer1177, p-eNOSThr495, caveolin-1, extracellular signal-regulated kinase (ERK), p-ERK, Akt, p-AktSer473, Rho-associated coiled-coil protein kinase 1 (ROCK1), and vitamin D receptor were determined. Microparticle expression of eNOS and caveolin-1 were also determined. We found that under lowered oxygen condition, 1,25(OH)2D3 could upregulate EC eNOS, p-eNOSSer1177, and p-AktSer473 expression, but inhibit cleaved ROCK1 expression. The upregulatory and inhibitory effects induced by 1,25(OH)2D3 were dose dependent. Strikingly, we also found that oxidative stress-induced decrease in ratio of eNOS and caveolin-1 expression in MP could be attenuated when 1,25(OH)2D3 was present in culture. These results suggest that upregulation of eNOSSer1177 and AktSer473 phosphorylation and inhibition of ROCK1 cleavage in EC and modulation of eNOS and caveolin-1 expression in MP could be plausible mechanisms of vitamin D protective effects on ECs.

Summary Sentence

1,25(OH)2D3 induced upregulation of eNOSSer1177 and AktSer473 phosphorylation and inhibition of ROCK1 cleavage could be plausible mechanisms of vitamin D protective effects to suppress MP release by ECs.

© The Authors 2016. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please journals.permissions@oup.com
Xiuyue Jia, Jie Xu, Yang Gu, Xin Gu, Weimin Li, and Yuping Wang "Vitamin D suppresses oxidative stress-induced microparticle release by human umbilical vein endothelial cells," Biology of Reproduction 96(1), 199-210, (22 December 2016). https://doi.org/10.1095/biolreprod.116.142604
Received: 10 June 2016; Accepted: 15 November 2016; Published: 22 December 2016
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