Abstract 10929: Role of a Novel Adipocytokine CTRP9 in Regulation of Vascular Remodeling
Background: Obesity is a major risk factor for the development of vascular disorders including atherosclerosis and restenosis after angioplasty.C1q/TNF-related protein (CTRP) 9 is a novel adipocytokine that is downregulated in obese mice. Here, we investigated the effects of CTRP9 on neointimal hyperplasia and vascular smooth muscle cell (VSMC) proliferation in vivo and in vitro.
Methods and Results: An adenoviral vector expressing CTRP9 (Ad-CTRP9) or β-galactosidase as a control was injected into the jugular vein of wild-type (WT) mice 3 d prior to vascular injury. Left femoral arteries of mice were injured by a 0.015 inch stainless-steel wire inserted from the lumen. Administration of Ad-CTRP9 to WT mice increased plasma CTRP9 levels by a factor of 4.9 ± 0.7 at day 5 after injection compared with control. At 21 days after vascular injury, Ad-CTRP9 significantly attenuated the neointimal thickening compared with control (p<0.01, n=8). Ad-CTRP9 also decreased the number of bromodeoxyuridine (BrdU) positive proliferating cells in the neointima at day 7 after vascular injury (p<0.01, n=5). In cultured VSMCs, treatment with recombinant CTRP9 protein attenuated DNA synthesis induced by platelet-derived growth factor (PDGF)-BB as assessed by BrdU incorporation assay, and suppressed PDGF-BB-stimulated phosphorylation of ERK. Furthermore, CTRP9 treatment dose-dependently increased cAMP levels in VSMCs. Pretreatment with the adenylate cyclase inhibitor SQ22536 reversed the inhibitory effect of CTRP9 on PDGF-BB-stimulated DNA synthesis and ERK phosphorylation in VSMCs.
Conclusion: CTRP9 attenuates neointimal thickening after vascular injury and inhibits VSMC growth via cAMP-dependent mechanism. Thus, CTRP9 could be an important therapeutic target for the prevention of pathological vascular remodeling.
- © 2012 by American Heart Association, Inc.