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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1051.)
© 2006 American Heart Association, Inc.

Vascular Biology

Isolation and Characterization of Vasohibin-2 as a Homologue of VEGF-Inducible Endothelium-Derived Angiogenesis Inhibitor Vasohibin

Takumi Shibuya; Kazuhide Watanabe; Hiroshi Yamashita; Kazue Shimizu; Hiroki Miyashita; Mayumi Abe; Takuya Moriya; Hideki Ohta; Hikaru Sonoda; Tooru Shimosegawa; Koichi Tabayashi; Yasufumi Sato

From the Department of Vascular Biology (T.S., K.W., H.Y., K.S., H.M., M.A., Y.S.), Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan; the Department of Pathology (T.M.), Tohoku University Hospital, Sendai, Japan; Diagnostics Science Division (H.O., H.S.), Shionogi & Co, Ltd, Toyonaka, Japan; the Department of Gastroenterology (K.W., T.S.), Tohoku University Graduate School of Medicine, Sendai, Japan; and the Department of Cardiovascular Surgery (T.S.), Tohoku University Graduate School of Medicine, Sendai, Japan. Present address of Mayumi Abe: Department of Nanomedicine, Tokyo Medical and Dental University, Tokyo, Japan.

Correspondence to Yasufumi Sato, Department of Vascular Biology, Institute of Development, Aging, and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. E-mail y-sato{at}idac.tohoku.ac.jp

Objective— We recently isolated vasohibin, a novel vascular endothelial growth factor (VEGF)-inducible endothelium-derived angiogenesis inhibitor. Our aim is to find DNA sequences homologous to vasohibin and determine their expression profile.

Methods and Results— By the search of DNA sequences in the database, we found one homologous gene and designated it vasohibin-2. Overall amino acid sequence homology between the prototype vasohibin (vasohibin-1) and vasohibin-2 was >50%. Vasohibin-2 exhibited antiangiogenic activity. Vasohibin-2 expression in cultured endothelial cells was low and not inducible by the stimulation that induced vasohibin-1. However, the immunohistochemical analysis revealed that vasohibin-1 and -2 were diffusely expressed in endothelial cells in embryonic organs during mid-gestation. After that time point, vasohibin-1 and -2 became faint, but persisted to a certain extent in arterial endothelial cells from late gestation to neonate. Expression of vasohibin-1 and -2 could be augmented in vivo by local transfection with the VEGF gene in the embryonic brain or by cutaneous wounding in adult mice.

Conclusion— These results suggest that vasohibin-2, in combination with vasohibin-1, forms a novel family of angiogenesis inhibitors.

We found vasohibin-2 as a homologue of VEGF-inducible endothelium-derived angiogenesis inhibitor vasohibin. Vasohibin-2 exhibited antiangiogenic activity. Immunohistochemical analysis revealed that 2 vasohibins were ubiquitously expressed in endothelial cells in developing embryonic organs during mid-gestation. Vasohibin-2, in combination with vasohibin-1, forms a novel family of angiogenesis inhibitors.

Key Words: angiogenesis inhibitor • endothelial cells • vascular development • vasohibin

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