title: Epigallocatechin-3-gallate promotes angiogenesis via up-regulation of Nfr2 signaling pathway in a mouse model of ischemic stroke.
abstract: Epigallocatechin-3-gallate (EGCG) is the major effective component of green tea and has been known as a potential anticancer drug because of its antioxidant and anti-angiogenic properties. EGCG has also been reported to have preventive effects against ischemic stroke via nuclear factor erythroid 2-related factor 2 (Nfr2) signaling pathway, but how EGCG affect angiogenesis after stroke remains unclear. In this study, we investigated whether EGCG treatment in the acute phase of ischemic stroke can promote angiogenesis in a mouse model of transient middle cerebral artery occlusion (MCAO). We assessed neurological function with modified neurologic severity score (mNSS) test, infarct volume by Nessl staining, angiogenesis and oxidative stress by immunofluorescence analysis, intravital lectin perfusion analysis, western blot analysis and enzyme-linked immunosorbent assay (ELISA). In order to explore the role of Nrf2 in the angiogenesis of MCAO+EGCG-treated mice, we used MAPK/ERK inhibitor PD98059 to block the activation of Nrf2. We found MCAO+EGCG-treated mice had better neurologic outcome, less infarct volume, more number of Ki67/CD31-positive vessels, higher vascular density, unregulated VEGF-VEGFR2 signaling pathway, increased Nrf2 expression and decreased oxidative stress than did MCAO+vehicle-treated mice. Blocking Nrf2 with PD98059 significantly reduced the expression of Nrf2, increased oxidative stress and abolished the angiogenic and neuroprotective effects of EGCG on MCAO mice. We conclude that EGCG treatment in the early stage of ischemic stroke can promote angiogenesis in MCAO mice, possibly via upregulation of Nrf2 signaling pathway.
authors.affiliation: Anesthesiology Department, The Second Affiliated Hospital of ZhengZhou University, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Bai
authors.affiliation: Anesthesiology Department, The Third Affiliated Hospital of Zhengzhou University, China.
authors.forename: Zhipai
authors.initials: Z
authors.lastname: Lyu
authors.affiliation: Anesthesiology Department, The Second Affiliated Hospital of ZhengZhou University, China.
authors.forename: Xianhui
authors.initials: X
authors.lastname: Yang
authors.affiliation: Pharmacology Department, The Second Affiliated Hospital of ZhengZhou University, China.
authors.forename: Zhenjie
authors.initials: Z
authors.lastname: Pan
authors.affiliation: Neurology Department, The Second Affiliated Hospital of ZhengZhou University, China. Electronic address: drloujy@163.com.
authors.forename: Jiyu
authors.initials: J
authors.lastname: Lou
authors.affiliation: Anesthesiology Department, The Second Affiliated Hospital of ZhengZhou University, China. Electronic address: drdongtl@yeah.net.
authors.forename: Tieli
authors.initials: T
authors.lastname: Dong
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D005419:Flavonoids / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D005419:Flavonoids; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495636:Nfe2l2 protein, mouse; D047428:Protein Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D002392:Catechin; C045651:epigallocatechin gallate; C000592875:Kdr protein, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: Angiogenesis; EGCG; Ischemic stroke; Nrf2