RETRACTED: Enhancement of ischemia-induced angiogenesis by eNOS overexpression (Retracted Article)

被引:88
作者
Amano, K
Matsubara, H [1 ]
Iba, O
Okigaki, M
Fujiyama, S
Imada, T
Kojima, H
Nozawa, Y
Kawashima, S
Yokoyama, M
Iwasaka, T
机构
[1] Kansai Med Univ, Dept Med 2, Moriguchi, Osaka 5708507, Japan
[2] Kansai Med Univ, Ctr Cardiovasc, Moriguchi, Osaka 5708507, Japan
[3] Kobe Univ, Grad Sch Med, Div Cardiovasc & Resp Med, Kobe, Hyogo 657, Japan
关键词
endothelium; ischemia; nitric oxide synthase; nitric oxide; vasculature;
D O I
10.1161/01.HYP.0000053552.86367.12
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
It remains undetermined whether continuous endothelial nitric oxide (NO) overexpression exerts angiogenic action. We surgically induced hindlimb ischemia in transgenic mice overexpressing endothelial NO synthase in the endothelium (eNOS-Tg) and studied neocapillary formation, ischemia-induced vascular endothelial growth factor (VEGF) expression, cGMP accumulation, and Akt/PKB signaling. Laser Doppler imaging revealed a markedly increased recovery of blood perfusion in ischemic limbs of eNOS-Tg mice (44% increase) compared with that in wild-type mice. Angiography showed a marked increase in basal and ischemia-induced collateral vessel formation in eNOS-Tg mice. Basal capillary densities and tissue cGMP levels were increased in eNOS-Tg mice (1.8-fold and 1.6-fold versus wild-type mice, respectively). Ischemia-induced neocapillary formation and cGMP accumulation were markedly increased in eNOS-Tg mice (3.6-fold and 4.1-fold versus preischemia levels, respectively), whereas those in wild-type mice were much less (1.8-fold and 1.5-fold, respectively). Basal and time-dependent VEGF expression in ischemic muscles did not differ between eNOS-Tg and wild-type mice. Basal and VEGF-mediated Akt phosphorylation in aortas was similar between eNOS-Tg and wild-type mice. Aortic basal eNOS expression was increased 3.3-fold, and VEGF-mediated eNOS phosphorylation was markedly induced in aortas of eNOS-Tg compared with preischemia levels (4.2-fold), whereas much smaller changes were observed in wild-type mice (1.8-fold increase). Our study demonstrates that overexpression of eNOS protein causes a marked increase in neocapillary formation in response to tissue ischemia without affecting ischemia-induced VEGF expression or VEGF-mediated Akt phosphorylation.
引用
收藏
页码:156 / 162
页数:7
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