title: Adipose-derived factor CTRP9 attenuates vascular smooth muscle cell proliferation and neointimal formation.
abstract: Obesity is closely associated with the progression of vascular disorders, including atherosclerosis and postangioplasty restenosis. C1q/TNF-related protein (CTRP) 9 is an adipocytokine that is down-regulated in obese mice. Here we investigated whether CTRP9 modulates neointimal hyperplasia and vascular smooth muscle cell (VSMC) proliferation in vivo and in vitro. Left femoral arteries of wild-type (WT) mice were injured by a steel wire. An adenoviral vector expressing CTRP9 (Ad-CTRP9) or β-galactosidase as a control was intravenously injected into WT mice 3 d before vascular injury. Delivery of Ad-CTRP9 significantly attenuated the neointimal thickening and the number of bromodeoxyuridine-positive proliferating cells in the injured arteries compared with that of control. Treatment of VSMCs with CTRP9 protein attenuated the proliferative and chemotactic activities induced by growth factors including platelet-derived growth factor (PDGF)-BB, and suppressed PDGF-BB-stimulated phosphorylation of ERK. CTRP9 treatment dose-dependently increased cAMP levels in VSMCs. Blockade of cAMP-PKA pathway reversed the inhibitory effect of CTRP9 on DNA synthesis and ERK phosphorylation in response to PDGF-BB. The present data indicate that CTRP9 functions to attenuate neointimal formation following vascular injury through its ability to inhibit VSMC growth via cAMP-dependent mechanism, suggesting that the therapeutic approaches to enhance CTRP9 production could be valuable for prevention of vascular restenosis after angioplasty.
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Uemura
authors.forename: Rei
authors.initials: R
authors.lastname: Shibata
authors.forename: Koji
authors.initials: K
authors.lastname: Ohashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Enomoto
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kambara
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ogura
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yuasa
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Joki
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Megumi
authors.initials: M
authors.lastname: Miyabe
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kataoka
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ouchi
mesh_terms: D052242:Adiponectin / Q000502:physiology*; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000378:metabolism; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D017539:Tunica Intima / Q000254:growth & development*
chemical_list: D052242:Adiponectin; C543615:C1QTNF9B protein, human; D006023:Glycoproteins; D011994:Recombinant Proteins; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D048049:Extracellular Signal-Regulated MAP Kinases