title: Potential role of recombinant adeno-associated virus human thioredoxin-PR39 in cell and vascular protection against hypoxia.
abstract: The aim of the present study was to successfully construct a recombinant adeno-associated virus (rAAV) vector containing the human thioredoxin (hTRX)-PR39 chimeric gene (rAAV/hTRX-PR39), and verify that the vector was able to maintain a sustained, stable and efficient expression to achieve protein production in the cell. In the present study, a chicken embryo model was utilized to analyze the therapeutical effect of rAAV/hTRX-PR39 in cerebral ischemia diseases. ECV304 cells were transfected with rAAV/hTRX-PR39 and incubated under conditions of 20, 5 and 1% O2. Subsequently, the expression levels of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, fibroblast growth factor receptor (FGFR)-1 and syndecan-4 were detected by reverse transcription-quantitative polymerase chain reaction. Under hypoxic conditions, the mRNA expression levels of VEGF, VEGFR-1, VEGFR-2, FGFR-1 and syndecan-4 were found to increase in the PR39-transfected group when compared with the control group, while no statistically significant difference was observed between the PR39-transfected group and the control group under conditions of 20% O2. In addition, hTRX-PR39 was shown to increase the density of the vasculature and the survival rate of the chick embryos. Under hypoxic conditions, it was hypothesized that rAAV/hTRX-PR39 was capable of promoting angiogenesis, which may subsequently protect the cells from impairment by hypoxia. In conclusion, rAAV/hTRX-PR39 was demonstrated to promote vascularization and cell survival in hypoxia; thus, rAAV/hTRX-PR39 may have potential for use in therapy targeting cerebral ischemia.
authors.affiliation: Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Xi-Yun
authors.initials: XY
authors.lastname: Ruan
authors.affiliation: Department of Neurology, The Central Hospital of Tai'an, Tai'an, Shandong 271000, P.R. China.
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Liang
authors.affiliation: Department of Neurosurgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: DU
authors.affiliation: Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: You-Ting
authors.initials: YT
authors.lastname: Lin
authors.affiliation: Department of Neurosurgery, The Fifth Hospital of Jinan, Jinan, Shandong 250021, P.R. China.
authors.forename: Yu-Dong
authors.initials: YD
authors.lastname: Guo
authors.affiliation: Department of Neurology, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Ji-Feng
authors.initials: JF
authors.lastname: Li
authors.affiliation: Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Qin-Jian
authors.initials: QJ
authors.lastname: Sun
authors.affiliation: Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Yi-Feng
authors.initials: YF
authors.lastname: DU
keywords: angiogenesis; gene therapy; hypoxia; ischemia; recombinant adeno-associated virus/human thioredoxin-PR39