Induced angiogenesis under cerebral ischemia by cyclooxygenase 2 and hypoxia-inducible factor naked DNA in a rat indirect-bypass model

Abstract

We recently reported that hypoxic stress induces the expression of HIF-1α, HIF-2α, cyclooxygenases-2 (COX-2) and VEGF in vivo . In this study, we investigated whether HIF-1α, HIF-2α, or COX-2 naked DNA induced angiogenesis in a cerebral ischemic model in vivo. We utilized a rat encephalo-myo-synangiosis (EMS) model and inoculated naked DNA into the brain surface. We analyzed whether DNA induced angiogenic factors and neovascularization. New blood vessel formation was detected by anti-Factor VIII staining. A histological section treated with HIF-2α or COX-2 DNA showed an increased expression of VEGF with angiogenesis, in comparison to the control DNA. The HIF-1α, HIF-2α, and COX-2 are able to promote significant angiogenesis development. These results suggest the feasibility of a novel approach for therapeutic angiogenesis of cerebral ischemia in which neovascularization may be indirectly achieved using a transcriptional and cytokine's regulatory strategy.