Adipose‐derived protein omentin prevents neointimal formation after arterial injury. Issue 1 (9th October 2014) - Uemura, Yusuke
Abstract : Obesity is highly linked with the development of vascular diseases. Omentin is a circulating adipokine that is downregulated in patients with cardiovascular diseases. In this study, we investigated the role of omentin in regulation of vascular remodeling in response to injury. Wild‐type (WT) mice were treated intravenously with adenoviral vectors encoding human omentin (Ad‐OMT) or control β‐gal and subjected to arterial wire injury. Ad‐OMT treatment reduced the neointimal thickening and the frequencies of bromodeoxyuridine‐positive proliferating cells in injured arteries. Treatment of vascular smooth muscle cells (VSMCs) with human omentin protein at a physiologic concentration led to suppression of growth and ERK phosphorylation after stimulation with various growth factors. Omentin stimulated AMPK signaling in VSMCs, and blockade of AMPK reversed omentin‐mediated inhibition of VSMC growth and ERK phosphorylation. Furthermore, fat‐specific human omentin transgenic (OMT‐TG) mice exhibited reduced neointimal thickening and vascular cell growth following vascular injury. AMPK activation was enhanced in injured arteries in OMT‐TG mice, and administration of AMPK inhibitor reversed the reduction of neointimal hyperplasia in OMT‐TG mice. These data indicate that omentin attenuates neointimal formation after arterial injury and suppresses VSMC growth through AMPK‐dependent mechanisms. Thus, omentin can represent a novel target molecule for the prevention of vascular disorders.—Uemura, Y., Shibata, R., Kanemura, N., Ohashi, K., Kambara, T., Hiramatsu‐Ito, M., Enomoto, T., Yuasa, D., Joki, Y., Matsuo, K., Ito, M., Hayakawa, S., Ogawa, H., Murohara, T., Ouchi, N., Adipose‐derived protein omentin prevents neointimal formation after arterial injury. FASEB J. 29, 141–151 (2015). www.fasebj.org