title: Adipose-derived protein omentin prevents neointimal formation after arterial injury.
abstract: Obesity is highly linked with the development of vascular diseases. Omentin is a circulating adipokine that is downregulated in patients with cardiovascular diseases. In this study, we investigated the role of omentin in regulation of vascular remodeling in response to injury. Wild-type (WT) mice were treated intravenously with adenoviral vectors encoding human omentin (Ad-OMT) or control β-gal and subjected to arterial wire injury. Ad-OMT treatment reduced the neointimal thickening and the frequencies of bromodeoxyuridine-positive proliferating cells in injured arteries. Treatment of vascular smooth muscle cells (VSMCs) with human omentin protein at a physiologic concentration led to suppression of growth and ERK phosphorylation after stimulation with various growth factors. Omentin stimulated AMPK signaling in VSMCs, and blockade of AMPK reversed omentin-mediated inhibition of VSMC growth and ERK phosphorylation. Furthermore, fat-specific human omentin transgenic (OMT-TG) mice exhibited reduced neointimal thickening and vascular cell growth following vascular injury. AMPK activation was enhanced in injured arteries in OMT-TG mice, and administration of AMPK inhibitor reversed the reduction of neointimal hyperplasia in OMT-TG mice. These data indicate that omentin attenuates neointimal formation after arterial injury and suppresses VSMC growth through AMPK-dependent mechanisms. Thus, omentin can represent a novel target molecule for the prevention of vascular disorders.
authors.affiliation: Departments of Cardiology and.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Uemura
authors.affiliation: Departments of Cardiology and nouchi@med.nagoya-u.ac.jp rshibata@med.nagoya-u.ac.jp.
authors.forename: Rei
authors.initials: R
authors.lastname: Shibata
authors.affiliation: Departments of Cardiology and.
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Kanemura
authors.affiliation: Molecular Cardiovascular Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ohashi
authors.affiliation: Departments of Cardiology and.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kambara
authors.affiliation: Departments of Cardiology and.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Hiramatsu-Ito
authors.affiliation: Departments of Cardiology and.
authors.forename: Takashi
authors.initials: T
authors.lastname: Enomoto
authors.affiliation: Departments of Cardiology and.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yuasa
authors.affiliation: Departments of Cardiology and.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Joki
authors.affiliation: Departments of Cardiology and.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Departments of Cardiology and.
authors.forename: Masanori
authors.initials: M
authors.lastname: Ito
authors.affiliation: Departments of Cardiology and.
authors.forename: Satoko
authors.initials: S
authors.lastname: Hayakawa
authors.affiliation: Departments of Cardiology and.
authors.forename: Hayato
authors.initials: H
authors.lastname: Ogawa
authors.affiliation: Departments of Cardiology and.
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.affiliation: Molecular Cardiovascular Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan nouchi@med.nagoya-u.ac.jp rshibata@med.nagoya-u.ac.jp.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ouchi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000273:Adipose Tissue / Q000502:physiology; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005263:Femoral Artery / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology; D058851:GPI-Linked Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D037102:Lectins / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D032389:Myocytes, Smooth Muscle / Q000473:pathology / Q000502:physiology; D058426:Neointima / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D066253:Vascular Remodeling / Q000502:physiology
chemical_list: D016207:Cytokines; D058851:GPI-Linked Proteins; C432397:ITLN1 protein, human; D037102:Lectins; D048049:Extracellular Signal-Regulated MAP Kinases; D055372:AMP-Activated Protein Kinases
keywords: AMPK; VSMC; remodeling