title: Adrenomedullin provokes endothelial Akt activation and promotes vascular regeneration both in vitro and in vivo.
abstract: We previously reported that adrenomedullin (AM), a vasodilating hormone secreted from blood vessels, promotes proliferation and migration of human umbilical vein endothelial cells (HUVECs). In this study, we examined the ability of AM to promote vascular regeneration. AM increased the phosphorylation of Akt in HUVECs and the effect was inhibited by the AM antagonists and the inhibitors for protein kinase A (PKA) or phosphatidylinositol 3-kinase (PI3K). AM promoted re-endothelialization in vitro of wounded monolayer of HUVECs and neo-vascularization in vivo in murine gel plugs. These effects were also inhibited by the AM antagonists and the inhibitors for PKA or PI3K. The findings suggest that AM plays significant roles in vascular regeneration, associated with PKA- and PI3K-dependent activation of Akt in endothelial cells, and possesses therapeutic potential for vascular injury and tissue ischemia.
authors.affiliation: Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho Sakyo-ku, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Miyashita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
authors.forename: Naoki
authors.initials: N
authors.lastname: Sawada
authors.forename: Yasutomo
authors.initials: Y
authors.lastname: Fukunaga
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Sone
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yamahara
authors.forename: Takami
authors.initials: T
authors.lastname: Yurugi-Kobayashi
authors.forename: Kwijun
authors.initials: K
authors.lastname: Park
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
mesh_terms: D053607:Adrenomedullin; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology; D015153:Blotting, Western; D002455:Cell Division; D002465:Cell Movement; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004727:Endothelium / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology*; D004789:Enzyme Activation; D006801:Humans; D007797:Laminin / Q000494:pharmacology; D051379:Mice; D018919:Neovascularization, Physiologic; D010455:Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases; D011509:Proteoglycans / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D012038:Regeneration; D013997:Time Factors; D014945:Wound Healing
chemical_list: D053607:Adrenomedullin; D001672:Biocompatible Materials; D003094:Collagen; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D004338:Drug Combinations; D007797:Laminin; D010455:Peptides; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011509:Proteoglycans; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C059485:matrigel; C494918:AKT1 protein, human