| Autor: |
Uemura, Yusuke, Shibata, Rei, Ohashi, Koji, Enomoto, Takashi, Kambara, Takahiro, Yamamoto, Takashi, Ogura, Yasuhiro, Yuasa, Daisuke, Joki, Yusuke, Matsuo, Kazuhiro, Miyabe, Megumi, Kataoka, Yoshiyuki, Murohara, Toyoaki, Ouchi, Noriyuki |
| Předmět: |
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| Zdroj: |
FASEB Journal; Jan2013, Vol. 27 Issue 1, p25-33, 9p |
| Abstrakt: |
Obesity is closely associated with the progression of vascular disorders, including atherosclerosis and postangioplasty restenosis. Clq/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 v/tro. 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 bromode-oxyuridine-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-sfmulated phosphorylafion 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 [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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