Nitric Oxide Induces Vascular Endothelial Growth Factor Expression in the Rat Placenta<i>in Vivo</i>and<i>in Vitro</i>

Abe, Hideaki; Ishikawa, Wataru; Kushima, Takahiro; Nishimura, Tomoka; Mori, Chiemi; Onuki, Atsushi; Suzuki, Takehito; Ishíi, Yasuo; Kansaku, Norio; Miyazaki, Yoko; Tanaka, Kazuaki; Takizawa, Takeo

doi:10.1271/bbb.120923

Cited by 19 publications

(14 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…50,51 Butylscopolamine administration averted the late phase of colitis; that is, the DAI remained low and colonic mucosa ulceration was not observed, whereas the leakage of RITC-gelatin from vessels and arrest of cell proliferation in the crypt were still observed. The downregulation of iNOS by butylscopolamine might reduce VEGF-A expression, as reported by Abe et al 52 The inhibitory effect of butylscopolamine on DSS-colitis might be exerted partly by the downregulation of VEGF-A. These results suggest that neuronal iNOS participated in exacerbating inflammation and that butylscopolamine administration did not prevent the early phase of the DSS-induced colitis such as microangiopathy and hypoxia condition of tissues, but did inhibit the exacerbation of inflammation and vascular hyperpermeability by reducing neuronal excitation.…”

Section: Discussionsupporting

confidence: 60%

Microangiopathy triggers, and inducible nitric oxide synthase exacerbates dextran sulfate sodium-induced colitis

Saijo

Tatsumi

Arihiro

et al. 2015

Laboratory Investigation

View full text Add to dashboard Cite

Ulcerative colitis (UC) is a representative clinical manifestation of inflammatory bowel disease that causes chronic gastrointestinal tract inflammation. Dextran sulfate sodium (DSS)-induced colitis mice have been used to investigate UC pathogenesis, and in this UC model, disturbance and impairment of the mucosal epithelium have been reported to cause colitis. However, how DSS sporadically breaks down the epithelium remains unclear. In this study, we focused on the colonic microcirculation and myenteric neurons of DSS-induced colitis. Moreover, we examined the potential of myenteric neurons as a target to prevent exacerbation of colitis. Fluorescent angiographic and histopathological studies revealed that DSS administration elicited blood vessel disruption before epithelial disorders appeared. Ischemic conditions in the lamina propria induced inducible nitric oxide synthase (iNOS) expression in myenteric neurons as colitis aggravated. When neuronal activity was inhibited with butylscopolamine, neuronal iNOS expression decreased, and the exacerbation of colitis was prevented. These results suggested that DSS-induced colitis was triggered by microcirculatory disturbance in the mucosa, and that excessive neuronal excitation aggravated colitis. During remission periods of human UC, endoscopic inspection of the colonic microcirculation may enable the early detection of disease recurrence, and inhibition of neuronal iNOS expression may prevent the disease from worsening.

show abstract

Section: Discussionsupporting

confidence: 60%

Microangiopathy triggers, and inducible nitric oxide synthase exacerbates dextran sulfate sodium-induced colitis

Saijo

Tatsumi

Arihiro

et al. 2015

Laboratory Investigation

View full text Add to dashboard Cite

show abstract

“…We showed that EC-specific VEGF levels decrease in the absence of iNOS expression or activity and increase in the presence of an NO donor, and that this occurs in direct correlation with metastatic success [11]. iNOS-dependent VEGF production has also been reported elsewhere [64, 69, 70]. …”

Section: Introductionmentioning

confidence: 69%

Endothelial hypoxic metabolism in carcinogenesis and dissemination : HIF-A isoforms are a NO metastatic phenomenon

2013

View full text Add to dashboard Cite

Tumor biology is a broad and encompassing field of research, particularly given recent demonstrations of the multicellular nature of solid tumors, which have led to studies of molecular and metabolic intercellular interactions that regulate cancer progression. Hypoxia is a broad stimulus that results in activation of hypoxia inducible factors (HIFs). Downstream HIF targets include angiogenic factors (e.g. vascular endothelial growth factor, VEGF) and highly reactive molecules (e.g. nitric oxide, NO) that act as cell-specific switches with unique spatial and temporal effects on cancer progression. The effect of cell-specific responses to hypoxia on tumour progression and spread, as well as potential therapeutic strategies to target metastatic disease, are currently under active investigation. Vascular endothelial remodelling events at tumour and metastatic sites are responsive to hypoxia, HIF activation, and NO signalling. Here, we describe the interactions between endothelial HIF and NO during tumor growth and spread, and outline the effects of endothelial HIF/NO signalling on cancer progression. In doing so, we attempt to identify areas of metastasis research that require attention, in order to ultimately facilitate the development of novel treatments that reduce or prevent tumour dissemination.

show abstract

“…VEGF is an important growth factor for angiogenesis during lung development. It was reported that NO induces VEGF synthesis (37), and VEGF induces EPCs mobilization and migration and incorporation into damaged vessels (20). We Figure 6.…”

Section: Lung Enos and Vegf Were Increased When Combining Epcs Transpmentioning

confidence: 87%

Combined iNO and endothelial progenitor cells improve lung alveolar and vascular structure in neonatal rats exposed to prolonged hyperoxia

Sun

Qian

2015

Pediatr Res

View full text Add to dashboard Cite

Background: Stem cells or inhaled nitric oxide (iNO) are reported to improve lung structures in bronchopulmonary dysplasia (BPD) models. We hypothesized that combined iNO and transplanted endothelial progenitor cells (EPCs) might restore lung structure in rats after neonatal hyperoxia. Methods: Litters were separated into eight groups: room air, hyperoxia, hyperoxia + iNO, hyperoxia + iNO + L-NAME, hyperoxia + EPCs, hyperoxia + EPCs + L-NAME, hyperoxia + EPCs + iNO, and hyperoxia + EPCs + iNO + L-NAME. Litters were exposed to hyperoxia from the 21st day, then, sacrificed. EPCs were injected on the 21st day. L-NAME was injected daily for 7 d from the 21st day. Serum vascular endothelial growth factor (VEGF), radial alveolar count (RAC), VIII factor, EPCs engraftment, lung VEGF, VEGFR2, endothelial nitric oxide (eNOS) and SDF-1 expression, and NO production were examined. results: Hyperoxia exposure led to air space enlargement, loss of lung capillaries, and low expression of VEGF and eNOS. Transplanted EPCs, when combined with iNO, had significantly increased engraftment in lungs, compared to EPCs alone, upon hyperoxia exposure. There was improvement in alveolarization, microvessel density, and upregulation of VEGF and eNOS proteins in the hyperoxia-exposed EPCs with iNO group, compared to hyperoxia alone. conclusion: Combined EPCs and iNO improved lung structures after neonatal hyperoxia. This was associated with the upregulation of VEGF and eNOS expression.B ronchopulmonary dysplasia (BPD) is a chronic lung disease associated with significant mortality and morbidity in premature infants. New BPD is characterized by arrested alveolar and vascular growth (vascular hypothesis of BPD) (1,2). Alveolar formation is a highly coordinated process between the development of airways and pulmonary vasculature (3). Exposure to inflammation caused by excessive O 2 supplementation is hypothesized to interfere with the coordinated process of normal human lung development. Neonatal hyperoxia exposure is known to disrupt alveolar formation and growth, providing a useful model for studying BPD (4).Cell-based therapy is a novel approach that offers much promise in the prevention and treatment of BPD, including embryonic stem cells, mesenchymal stem cells, placental stem cells, umbilical cord stem cells, amniotic fluid and amnionderived cells, and lung progenitor cells. Endothelial progenitor cells (EPCs) are precursors of endothelial cells, which have the capacity of self-renewal and proliferation. EPCs is one of the key cells mediating vascular growth, which can mobilize from bone marrow and home to the site of vascular injuries, promoting neovascularization (5). There is data showing that reduced numbers or dysfunction of EPCs at birth is associated with the development of BPD (6,7). In addition, a reduction in the number of EPCs in the bone marrow, circulation and lungs has also emerged in animal models of BPD (8). Evidences that angiogenic cells treatment can restore lung structure have been demonstrated. Balasubramaniam et al...

show abstract

Nitric Oxide Induces Vascular Endothelial Growth Factor Expression in the Rat Placentain Vivoandin Vitro

Cited by 19 publications

References 41 publications

Microangiopathy triggers, and inducible nitric oxide synthase exacerbates dextran sulfate sodium-induced colitis

Microangiopathy triggers, and inducible nitric oxide synthase exacerbates dextran sulfate sodium-induced colitis

Endothelial hypoxic metabolism in carcinogenesis and dissemination : HIF-A isoforms are a NO metastatic phenomenon

Combined iNO and endothelial progenitor cells improve lung alveolar and vascular structure in neonatal rats exposed to prolonged hyperoxia

Contact Info

Product

Resources

About