Induced angiogenesis under cerebral ischemia by cyclooxygenase 2 and hypoxia-inducible factor naked DNA in a rat indirect-bypass model.
We recently reported that hypoxic stress induces the expression of HIF-1alpha, HIF-2alpha, cyclooxygenases-2 (COX-2) and VEGF in vivo. In this study, we investigated whether HIF-1alpha, HIF-2alpha, 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-2alpha or COX-2 DNA showed an increased expression of VEGF with angiogenesis, in comparison to the control DNA. The HIF-1alpha, HIF-2alpha, 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.
Anan
Mitsuhiro
M
Department of Neurosurgery, Oita University School of Medicine, Idaigaoka 1-1, Hasama, Yufu, Oita 879-5593, Japan.
Abe
Tatsuya
T
Matsuda
Takeshi
T
Ishii
Keisuke
K
Kamida
Tohru
T
Fujiki
Minoru
M
Kobayashi
Hidenori
H
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D002545:Brain Ischemia / Q000473:pathology / Q000628:therapy; D051546:Cyclooxygenase 2 / Q000235:genetics*; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics*; D005169:Factor VIII; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D007150:Immunohistochemistry; D007763:Lac Operon / Q000235:genetics; D008297:Male; D018919:Neovascularization, Physiologic / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D051546:Cyclooxygenase 2; D004247:DNA; D005169:Factor VIII; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D000099162:Endothelial PAS Domain-Containing Protein 1