Nitric oxide is involved in the regulation of angiogenesis

Pipili-Synetos, Eva; Sakkoula, Eleni; Maragoudakis, Michael E.

doi:10.1111/j.1476-5381.1993.tb13476.x

Cited by 99 publications

(54 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lau and Ma 26 reported that NO inhibits migration of cultured endothelial cells. Pipili-Synetos et al 27 reported that NO donors inhibit angiogenesis in the chick chorioallantoic membrane and tube formation. In contrast, Guo et al 28 reported that an NO donor stimulated the proliferation of aortic endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of Ischemia-Induced Angiogenesis by eNOS Overexpression

et al. 2003

View full text Add to dashboard Cite

Abstract-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.

show abstract

Section: Discussionmentioning

confidence: 99%

Enhancement of Ischemia-Induced Angiogenesis by eNOS Overexpression

et al. 2003

View full text Add to dashboard Cite

show abstract

“…NO has been implicated in angiogenesis on the basis of observations in dierent models of angiogenesis, including the chick chorioallantoic membrane (Pipili-Synetos et al, 1993), the rabbit cornea (Ziche et al, 1993b) and dierent tumour types (Gallo et al, 1998). However, these studies oer con¯icting conclusions as to whether NO promotes or inhibits angiogenesis.…”

Section: Discussionmentioning

confidence: 88%

“…Nitric oxide (NO), a mediator with a complex pro®le of biological activity was ®rst implicated in angiogenesis by Pipili-Synetos et al (1993) who reported that the nitric oxide synthase (NOS) inhibitor, nitro-L-arginine methyl ester (L-NAME) enhanced vessel growth in the chick chorioallantoic membrane (CAM) model (Pipili-Synetos et al, 1993). Additional studies indicated that NO donors reduced tissue angiogenesis and tumour neovascularization (Pipili-Synetos et al, 1995;Sakkoula et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Inducible nitric oxide synthase (iNOS) activity promotes ischaemic skin flap survival

Kane

Barker

Mitchell

et al. 2001

British J Pharmacology

View full text Add to dashboard Cite

1 We have examined the role of nitric oxide (NO) in a model of functional angiogenesis in which survival of a skin¯ap depends entirely on angiogenesis to provide an arterial blood supply to maintain tissue viability. 2 The dierent eects of nitric oxide synthase (NOS) inhibitors on rat skin¯ap survival appeared to be explained on the basis of their NOS isoform selectivity. Skin¯ap survival was decreased by iNOS-selective (inducible NOS) inhibitors, S-methyl-isothiourea, aminoguanidine and aminoethylthiorea; unaected by the non-selective inhibitor nitro-imino-L-ornithine; and enhanced by the cNOS (constitutive NOS, that is endothelial NOS (eNOS) and neuronal NOS (nNOS)) inhibitor, nitro-L-arginine methyl ester. 3 Skin¯ap survival was reduced in mice with targeted disruption of the iNOS gene (iNOS knockout mice), and the administration of nitro-L-arginine methyl ester signi®cantly increased¯ap survival in iNOS knockout mice (P50.05). 4 iNOS immunoreactivity was identi®ed in mast cells in the angiogenic region. Immunoreactive vascular endothelial growth factor (VEGF) and basic ®broblast growth factor were also localized to mast cells. 5 The combination of interferon-g and tumour necrosis factor-a induced NO production and increased VEGF levels in mast cells cultured from bone marrow of wild-type, but not iNOS KO mice. 6 The increased tissue survival associated with the capacity for iNOS expression may be related to iNOS-dependent enhancement of VEGF levels and an ensuing angiogenic response. Our results provide both pharmacological and genetic evidence that iNOS activity promotes survival of ischaemic tissue.

show abstract

“…NO production by tumour cells may influence tumour growth and metastasis (Pipili-Synetos et al, 1993;Jenkins et al, 1995). The functions of NO in tumours potentially facilitate tumour growth.…”

Section: Discussionmentioning

confidence: 99%

Serum concentrations of vascular endothelial growth factor and nitrite as an estimate of in vivo nitric oxide in patients with gastric cancer

Eroğlu¹,

Demirci²,

Ayyildiz³

et al. 1999

Br J Cancer

View full text Add to dashboard Cite

SummaryThe importance of tumour angiogenesis in the process of tumour growth and progression in solid tumours has been widely accepted. Among many angiogenic factors, vascular endothelial growth factor (VEGF) has been shown to play a major role in the development and dissemination of the malignant tumours. Nitric oxide (NO) production was also observed in solid tumour tissues. NO has been reported to play an important role for the mitogenic effect of VEGF in the angiogenic process. However, little is known about the correlation between VEGF and NO in circulating levels. Therefore, we investigated serum VEGF and NO concentrations in human gastric cancers as well as healthy individuals, and examined the influence of tumour stage on circulating level of VEGF. The study consisted of 11 healthy individuals and 37 patients with primary gastric cancer who did not receive any prior therapy. Patients were categorized into four groups according to TNM classification. The level of VEGF 165 in preoperative sera of gastric cancer patients and healthy donors was assayed using the quantitative sandwich enzyme immunoassay technique. NO concentration was estimated indirectly from serum nitrite. The ANOVA test showed a significant difference in serum VEGF 165 concentrations between tumour stages (P < 0.001). A striking relationship was found between serum NO levels and tumour stage (P < 0.001). A significant difference was also seen between healthy individuals and patients with stage 1 disease. The present study suggested that large tumour burden was associated with significantly increased levels of VEGF 165 and NO.

show abstract

Nitric oxide is involved in the regulation of angiogenesis

Cited by 99 publications

References 7 publications

Enhancement of Ischemia-Induced Angiogenesis by eNOS Overexpression

Enhancement of Ischemia-Induced Angiogenesis by eNOS Overexpression

Inducible nitric oxide synthase (iNOS) activity promotes ischaemic skin flap survival

Serum concentrations of vascular endothelial growth factor and nitrite as an estimate of in vivo nitric oxide in patients with gastric cancer

Contact Info

Product

Resources

About