Adipose-derived factor CTRP9 attenuates vascular smooth muscle cell proliferation and neointimal formation

作者：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

来源：The FASEB Journal, 2013, 27(1): 25-33.

DOI：10.1096/fj.12-213744

• adipocytokine
• vascular remodeling
• cAMP

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 beta-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-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.-Uemura, Y., Shibata, R., Ohashi, K., Enomoto, T., Kambara, T., Yamamoto, T., Ogura, Y., Yuasa, D., Joki, Y., Matsuo, K., Miyabe, M., Kataoka, Y., Murohara, T., Ouchi, N. Adipose-derived factor CTRP9 attenuates vascular smooth muscle cell proliferation and neointimal formation. FASEB J. 27, 25-33 (2013). www.fasebj.org

• 出版日期2013-1