Nitric oxide regulates Angiopoietin1/Tie2 expression after stroke.
We tested whether the nitric oxide donor, (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) aminio] diazen-1-ium-1,2-diolate (DETA-NONOate), increases expression of Angiopoietin (Ang1)/Tie2, which may play a role in regulating angiogenesis and vascular integrity after stroke in rats. Wistar rats were subjected to middle cerebral artery occlusion and treated with or without DETA-NONOate. Stroke rats treated with DETA-NONOate show significantly increased Ang1, Tie2 and Occludin expression in the ischemic border compared with control stroke animals (p < 0.05). Consistent with in vivo data, DETA-NONOate promotes capillary tube formation in cultured brain endothelial cells. Neutralizing Ang1 antibody attenuates DETA-NONOate-induced capillary tube formation. The data suggest that the Ang1/Tie2 axis promotes DETA-NONOate-induced angiogenesis and stabilizes of angiogenic vessels after stroke.
Zacharek
Alex
A
Department of Neurology, Henry Ford Health Sciences Center, Detroit, MI 48202, USA.
Chen
Jieli
J
Zhang
Chunling
C
Cui
Xu
X
Roberts
Cynthia
C
Jiang
Hao
H
Teng
Hua
H
Chopp
Michael
M
D042683:Angiopoietin-1 / Q000235:genetics*; D000818:Animals; D005786:Gene Expression Regulation; D008297:Male; D020768:Middle Cerebral Artery; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D042787:Receptor, TIE-2 / Q000235:genetics*; D020521:Stroke / Q000235:genetics / Q000503:physiopathology*
D042683:Angiopoietin-1; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D012333:RNA, Messenger; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine; D042787:Receptor, TIE-2