title: Angiogenic roles of adrenomedullin through vascular endothelial growth factor induction.
abstract: Recently, we have reported that a vasoactive peptide adrenomedullin promotes angio/arteriogenesis and prevents cognitive decline after chronic cerebral hypoperfusion in mice. Adrenomedullin upregulated brain levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor, although the regulation mechanism needs to be determined. In this study, we showed that VEGF neutralization partially suppressed adrenomedullin-induced neovascularization and cognitive restoration in vivo. In-vitro, adrenomedullin promoted capillary tube formation of the cultured endothelium, whereas VEGF neutralization abolished these effects. Adrenomedullin was found to upregulate VEGF and basic fibroblast growth factor through the adrenomedullin receptor and the phosphatidylinositol 3-kinase pathway. These results suggest that adrenomedullin has potential as therapy for dementia through enhancement of functional vascular growth.
authors.affiliation: Departments of Neurology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Takakuni
authors.initials: T
authors.lastname: Maki
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ihara
authors.forename: Youshi
authors.initials: Y
authors.lastname: Fujita
authors.forename: Takuo
authors.initials: T
authors.lastname: Nambu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Harada
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Ito
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Tomimoto
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
mesh_terms: D053607:Adrenomedullin / Q000378:metabolism*; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D042783:Endothelial Cells; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic; D015398:Signal Transduction / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D016222:Fibroblast Growth Factor 2; D053607:Adrenomedullin