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Effect of the Recombinant Adenovirus-Mediated HIF-1 Alpha on the Expression of VEGF in the Hypoxic Brain Microvascular Endothelial Cells of Rats

Authors Jin ML, Zou ZH, Tao T, Li J, Xu J, Luo KJ, Liu Z

Received 15 November 2019

Accepted for publication 13 January 2020

Published 7 February 2020 Volume 2020:16 Pages 397—406

DOI https://doi.org/10.2147/NDT.S238616

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Yuping Ning


Ming-Lu Jin, 1–3,* Zhe-Hua Zou, 1, 4,* Tao Tao, 1 Jun Li, 3, 5 Jian Xu, 3 Kai-Jian Luo, 6 Zhi Liu 7

1Department of Rehabilitation Medicine, Guizhou Provincial People’s Hospital, Guiyang, Guizhou 550002, People’s Republic of China; 2Department of Neurology, Qijiang Hospital of the First Affiliated Hospital of Chongqing Medical University, Chongqing 404100, People’s Republic of China; 3Department of Neurology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550001, People’s Republic of China; 4Department of General Practice, The First Hospital of Qinhuangdao, Qinhuangdao, Hebei 066000, People’s Republic of China; 5Department of Neurology, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, People’s Republic of China; 6Guizhou Cancer Hospital, Guiyang, Guizhou 550000, People’s Republic of China; 7Department of Pharmacy, The Affiliated Hospital Guizhou Medical University, Guiyang, Guizhou 550001, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Tao Tao
Department of Rehabilitation Medicine, Guizhou Provincial People’s Hospital, Guiyang, Guizhou 550002, People’s Republic of China
Email taotao62824@sina.com

Objective: To investigate the effect of recombinant adenovirus-mediated HIF-1 alpha (HIF-1α) on the expression of vascular endothelial growth factor (VEGFA) and HIF-1α in hypoxic brain microvascular endothelial cells (BMEC) in rats.
Methods: Primary cultured rat BMEC in vitro were treated without or with either recombinant adenovirus-mediated hypoxia-inducible factor-1 alpha (AdHIF-1α) or recombinant adenovirus empty vector (Ad) in the presence of CoCl 2 (simulating hypoxia conditions), or were grown under normoxia conditions. The expression of VEGFA and HIF-1α was analyzed at 12h, 24h, 48h and 72h incubation time, respectively. We also accessed a GEO dataset of stroke to analyze in vivo the alteration of HIF-1α and VEGFA expression, and the correlations between HIF-1α, VEGFA and CD31 mRNA levels in vascular vessels after stroke.
Results: VEGFA and HIF-1α expression were significantly higher in at each time point in the AdHIF-1α than other groups (p< 0.05), whereas the Ad group and hypoxia group, showed no statistically significant difference (p> 0.05). Moreover, VEGFA and HIF-1α levels were significantly higher in BMEC under hypoxia conditions than normoxia conditions (p < 0.05). Both HIF-1α and VEGFA expression significantly increased after stroke in vivo with 1.30 and 1.57 fold-change in log2, respectively. There were significantly positive associations between HIF-1α, VEGFA and CD31 mRNA levels in vivo after stroke.
Conclusion: Hypoxia-induced HIF-1α and VEGFA expression in vascular vessels, and recombinant AdHIF-1α could up-regulate VEGFA, and enhance HIF-1ααlevels in BMEC in vitro, which may play an important role in the recovery of stroke.

Keywords: AdHIF-1α, brain microvascular endothelial cells, hypoxia, VEGFA, stroke

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