on March 9, 2006
Published online before print March 9, 2006, doi: 10.1161/01.ATV.0000216747.66660.26
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Submitted on September 12, 2005
Accepted on January 19, 2006
Isolation and Characterization of Vasohibin-2 as a Homologue of VEGF-Inducible Endothelium-Derived Angiogenesis Inhibitor Vasohibin
Takumi Shibuya ;
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.
* To whom correspondence should be addressed. 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.
Key words: angiogenesis inhibitor • endothelial cells • vascular development • vasohibin
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