Neovascularization in an arterio‐venous loop‐containing tissue engineering chamber: role of NADPH oxidase

Jiang, Fan; Zhang, G.; Hashimoto, Ichiro; Kumar, Beena S.; Bortolotto, Susan K.; Morrison, Wayne A.; Dusting, Gregory J.

doi:10.1111/j.1582-4934.2008.00199.x

Cited by 31 publications

(35 citation statements)

References 38 publications

(57 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is not the first instance we have reported a role for Nox2 in vascular sprouting. Using a chamber model of arterial venous loop re-construction, we have shown a high level of Nox2 expressed in endothelial cells of newly developed blood vessels sprouting from the loop and local administration of Nox inhibitors apocynin or gp91ds-tat peptide to the chamber suppressed angiogenesis [11]. It will be important to focus future studies on investigating the effects of long term treatments with specific Nox2 inhibitors or Nox2 deficient mice on angiogenesis after stroke to confirm the current findings.…”

Section: Resultssupporting

confidence: 58%

NADPH Oxidase and Angiogenesis Following Endothelin-1 Induced Stroke in Rats: Role for Nox2 in Brain Repair

et al. 2013

View full text Add to dashboard Cite

NADPH oxidases contribute to brain injury, yet they may also have a role in brain repair, particularly in vascular signaling and angiogenesis. This study determined the temporal and spatial profile of NADPH oxidase subunit expression/activity concurrently with angiogenesis in the brain following transient ischemic stroke induced by prolonged constriction of the middle cerebral artery by perivascular injection of endothelin-1 in conscious Hooded Wistar rats (n = 47). VEGF mRNA expression was increased in the ipsilateral cortex and striatum between 6 h and 28 days post-stroke concurrently with a marked increase in Nox2 mRNA expression up to 7 days, and increased Nox4 mRNA expression detected between 7 and 28 days. Point counting of blood vessels using Metamorph imaging software showed increased vascular sprouting between 3 and 7 days after stroke with new vascular networks detected in the core infarct region by 14 days. Angiogenic blood vessels 3 and 7 days post-stroke were observed to co-localise with both Nox2 antibody and dihydroethidium fluorescence suggesting a role for Nox2 generated superoxide during the phase of vascular remodeling, whilst Nox4 expression was detected once new cerebral vessels had formed. These results indicate for the first time that ROS signaling through a cerebrovascular Nox2 NADPH oxidase may be important in initiating brain angiogenesis.

show abstract

Section: Resultssupporting

confidence: 58%

NADPH Oxidase and Angiogenesis Following Endothelin-1 Induced Stroke in Rats: Role for Nox2 in Brain Repair

et al. 2013

View full text Add to dashboard Cite

show abstract

“…The NADPH oxidase family of ROS-generating enzymes is the key source of ROS in the vascular system and these enzyme complexes are crucial players in both physiological and pathological angiogenesis [32,33]. We have previously demonstrated that NADPH oxidase facilitates angiogenic responses in wound healing in a variety of tissues in vivo [34,35]. Studies of the roles of different isoforms of NADPH oxidase with genetically modified animals and in vivo siRNA approaches have also highlighted the involvement of Nox in VEGF-dependent neovascularization of hypoxic retinas in animals with oxygen-induced retinopathy [16,28,36].…”

Section: Discussionmentioning

confidence: 98%

“…Chemical cautery-induced fibrovascular proliferation is reduced in Nox2-deficient mice as is indicated by lower burn severity scores at day 7, as well as reduced corneal neovascularization at days 7 and 14. Although it might be possible that the reductions in corneal neovascularization and Vegf-A observed in Nox2 KO mice were consequences of the less severe corneal cautery in these than in wild type mice, this is unlikely for several reasons: (1) corneal cautery was performed in accordance with a standardized protocol by a single experienced operator masked to the genotype of each mouse; (2) increased Nox2 expression and the generation of ROS are associated with the inflammatory response after tissue injury and regeneration [39][40][41].…”

Section: Discussionmentioning

confidence: 99%

NADPH oxidase 2 plays a role in experimental corneal neovascularization

et al. 2016

View full text Add to dashboard Cite

Corneal neovascularization, the growth of new blood vessels in the cornea, is a leading cause of vision impairment after corneal injury. Neovascularization typically occurs in response to corneal injury such as that caused by infection, physical trauma, chemical burns or in the setting of corneal transplant rejection. The NADPH oxidase enzyme complex is involved in cell signalling for wound-healing angiogenesis, but its role in corneal neovascularization has not been studied. We have now analysed the role of the Nox2 isoform of NADPH oxidase in corneal neovascularization in mice following chemical injury. C57BL/6 mice aged 8-14 weeks were cauterized with an applicator coated with 75% silver nitrate and 25% potassium nitrate for 8 s. Neovascularization extending radially from limbal vessels was observed in corneal whole-mounts from cauterized wild type mice and CD31+ vessels were identified in cauterized corneal sections at day 7. In contrast, in Nox2 knockout (Nox2 KO) mice vascular endothelial growth factor-A (Vegf-A), Flt1 mRNA expression, and the extent of corneal neovascularization were all markedly reduced compared with their wild type controls. The accumulation of Iba-1+ microglia and macrophages in the cornea was significantly less in Nox2 KO than in wild type mice. In conclusion, we have demonstrated that Nox2 is implicated in the inflammatory and neovascular response to corneal chemical injury in mice and clearly VEGF is a mediator of this effect. This work raises the possibility that therapies targeting Nox2 may have potential for suppressing corneal neovascularization and inflammation in humans.

show abstract

“…Besides, a Nox2-containing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is known to play a major role in hypoxia-driven angiogenesis. Recently, it could be confirmed that it is involved in the process of neoangiogenesis within the AV loop chamber and that specific inhibitors such as apocynin or gp91ds-tat peptide lead to an inhibition of further vessel growth [25]. …”

Section: The Arteriovenous Loop Model: Methods and Mechanism Behind Thmentioning

confidence: 99%

The Arteriovenous Loop: Engineering of Axially Vascularized Tissue

et al. 2018

View full text Add to dashboard Cite

Background: Most of the current treatment options for large-scale tissue defects represent a serious burden for the patients, are often not satisfying, and can be associated with significant side effects. Although major achievements have already been made in the field of tissue engineering, the clinical translation in case of extensive tissue defects is only in its early stages. The main challenge and reason for the failure of most tissue engineering approaches is the missing vascularization within large-scale transplants. Summary: The arteriovenous (AV) loop model is an in vivo tissue engineering strategy for generating axially vascularized tissues using the own body as a bioreactor. A superficial artery and vein are anastomosed to create an AV loop. This AV loop is placed into an implantation chamber for prevascularization of the chamber inside, e.g., a scaffold, cells, and growth factors. Subsequently, the generated tissue can be transplanted with its vascular axis into the defect site and anastomosed to the local vasculature. Since the blood supply of the growing tissue is based on the AV loop, it will be immediately perfused with blood in the recipient site leading to optimal healing conditions even in the case of poorly vascularized defects. Using this tissue engineering approach, a multitude of different axially vascularized tissues could be generated, such as bone, skeletal or heart muscle, or lymphatic tissues. Upscaling from the small animal AV loop model into a preclinical large animal model could pave the way for the first successful attempt in clinical application. Key Messages: The AV loop model is a powerful tool for the generation of different axially vascularized replacement tissues. Due to minimal donor site morbidity and the possibility to generate patient-specific tissues variable in type and size, this in vivo tissue engineering approach can be considered as a promising alternative therapy to current treatment options of large-scale defects.

show abstract

Neovascularization in an arterio‐venous loop‐containing tissue engineering chamber: role of NADPH oxidase

Cited by 31 publications

References 38 publications

NADPH Oxidase and Angiogenesis Following Endothelin-1 Induced Stroke in Rats: Role for Nox2 in Brain Repair

NADPH Oxidase and Angiogenesis Following Endothelin-1 Induced Stroke in Rats: Role for Nox2 in Brain Repair

NADPH oxidase 2 plays a role in experimental corneal neovascularization

The Arteriovenous Loop: Engineering of Axially Vascularized Tissue

Contact Info

Product

Resources

About