Isolation and characterization of vasohibin-2 as a homologue of VEGF-inducible endothelium-derived angiogenesis inhibitor vasohibin.
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.


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.


CONCLUSIONS
These results suggest that vasohibin-2, in combination with vasohibin-1, forms a novel family of angiogenesis inhibitors.
Shibuya
Takumi
T
Department of Vascular Biology, Institute of Development, Aging, and Cancer, Tohoku University, Sendai 980-8575, Japan.
Watanabe
Kazuhide
K
Yamashita
Hiroshi
H
Shimizu
Kazue
K
Miyashita
Hiroki
H
Abe
Mayumi
M
Moriya
Takuya
T
Ohta
Hideki
H
Sonoda
Hikaru
H
Shimosegawa
Tooru
T
Tabayashi
Koichi
K
Sato
Yasufumi
Y
D020533:Angiogenesis Inhibitors / Q000032:analysis / Q000235:genetics* / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020533:Angiogenesis Inhibitors; D012333:RNA, Messenger