Abstract 10928: The Adipokine Omentin Prevents the Pathological Vascular Remodeling
Background: Obese states are associated with the development of atherosclerosis and post-angioplasty restenosis. Omentin is an adipokine whose concentrations are reduced in obese subjects. We have reported that circulating omentin levels are down-regulated in patients with coronary artery disease. Here, we investigated the role of omentin on neointimal hyperplasia and vascular smooth muscle cell (VSMC) growth.
Methods and Results: An adenoviral vector encoding human omentin (Ad-OMT) or β-galactosidase as a control was injected into the jugular vein of wild-type mice 3 days prior to vascular injury. Left femoral arteries of mice were injured by a stainless-steel wire from the lumen. Although human omentin protein was not detectable in plasma in control mice, plasma human omentin levels were increased to 1353.9 ± 169.6 ng/ml in Ad-OMT-treated mice on the 5th day after injection. Administration of Ad-OMT-treated mice showed a significant reduction of the intimal/medial area ratio at 21 days after vascular injury compared with control (p<0.01, n=8). Ad-OMT reduced 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 omentin protein suppressed VSMC proliferation and migration induced by various growth factors such as PDGF and HB-EGF. Omentin also inhibited growth factor-induced phosphorylation of ERK in VSMCs. Treatment of VSMCs with omentin led to a time-dependent increase in AMPK phosphorylation. Furthermore, transduction with dominant-negative AMPK reversed the inhibitory effect of omentin on growth factor-stimulated VSMC proliferation and ERK phosphorylation.
Conclusion: Omentin attenuates neointimal hyperplasia after vascular injury and suppresses VSMC growth through its ability to activate AMPK, suggesting that omentin can represent a novel target molecule for the prevention of pathological arterial remodeling.
- © 2013 by American Heart Association, Inc.