Hypoxia-inducible factor-1alpha DNA induced angiogenesis in a rat cerebral ischemia model.
BACKGROUND
Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that regulates the adaptive response to hypoxia in mammalian cells. It consists of a regulatory subunit HIF-1alpha, which accumulates under hypoxic conditions, and a constitutively expressed subunit, HIF-1beta. In this study, we investigated HIF-1alpha naked DNA-induced angiogenesis in a cerebral ischemic model in vivo.


METHODS
We utilized a rat encephalo-myo-synangiosis (EMS) model and inoculated HIF-1alpha DNA into the brain surface or the temporal muscle. We analysed whether HIF-1alpha induced angiogenic factors and collateral circulation.


RESULTS
A histological section treated with HIF-1alpha DNA showed an increased expression of HIF1 a and VEGF with collateral circulation, in comparison with control DNA (p < 0.01). The HIF-1alpha transcription factor is able to promote significant angiogenesis development.


CONCLUSIONS
These results suggest the feasibility of a novel approach for therapeutic collateral circulation of cerebral ischemia in which neovascularization may be achieved indirectly using a transcriptional regulatory strategy.
Department of Neurosurgery, Oita University School of Medicine, Idaigaoka 1-1, Oita, 879-5593, Japan.
Takeshi
T
Matsuda
Tatsuya
T
Abe
Jian Liang
JL
Wu
Minoru
M
Fujiki
Hidenori
H
Kobayashi
D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology* / Q000628:therapy; D002452:Cell Count / Q000379:methods; D003097:Collateral Circulation / Q000187:drug effects* / Q000502:physiology; D004247:DNA / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009389:Neovascularization, Pathologic / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use*; D019444:Vaccines, DNA / Q000008:administration & dosage*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors; D019444:Vaccines, DNA; D042461:Vascular Endothelial Growth Factor A; D004247:DNA; D001616:beta-Galactosidase