Hypoxia-inducible factor-1alpha DNA induced angiogenesis in a rat cerebral ischemia model.

Abstract

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. CONCLUSION: 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.