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: Yusuke Uemura, Rei Shibata, Koji Ohashi, Takashi Enomoto, Takahiro Kambara, Takashi Yamamoto, Yasuhiro Ogura, Daisuke Yuasa, Yusuke Joki, Kazuhiro Matsuo, Megumi Miyabe, Yoshiyuki Kataoka, Toyoaki Murohara, Noriyuki Ouchi
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 27 Issue 1 Pg. 25-33 (Jan 2013) ISSN: 1530-6860 [Electronic] United States
• PMID: 22972916 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adiponectin
• C1QTNF9B protein, human
• Glycoproteins
• Recombinant Proteins
• Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
• Extracellular Signal-Regulated MAP Kinases

Topics

• Adiponectin (physiology)
• Adipose Tissue (metabolism)
• Animals
• Blotting, Western
• Cell Proliferation
• Cells, Cultured
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Glycoproteins (physiology)
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Muscle, Smooth, Vascular (cytology)
• Phosphorylation
• Recombinant Proteins (metabolism)
• Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
• Tunica Intima (growth & development)