)| PMID |
16877369 ( ) |
|---|---|
| Title | NADPH oxidase-derived overproduction of reactive oxygen species impairs postischemic neovascularization in mice with type 1 diabetes. |
| Abstract | We hypothesized that diabetes-induced oxidative stress may affect postischemic neovascularization. The response to unilateral femoral artery ligation was studied in wild-type or gp91(phox)-deficient control or type 1 diabetic mice or in animals treated with the anti-oxidant N-acetyl-l-cysteine (NAC) or with in vivo electrotransfer of a plasmid encoding dominant-negative Rac1 (50 microg) for 21 days. Postischemic neovascularization was reduced in diabetic mice in association with down-regulated vascular endothelial growth factor-A protein levels. In diabetic animals vascular endothelial growth factor levels and postischemic neovascularization were restored to nondiabetic levels by the scavenging of reactive oxygen species (ROS) by NAC administration or the inhibition of ROS generation by gp91(phox) deficiency or by administration of dominant-negative Rac1. Finally, diabetes reduced the ability of adherent bone marrow-derived mononuclear cells (BM-MNCs) to differentiate into endothelial progenitor cells. Treatment with NAC (3 mmol/L), apocynin (200 micromol/L), or the p38MAPK inhibitor LY333351 (10 micromol/L) up-regulated the number of endothelial progenitor cell colonies derived from diabetic BM-MNCs by 1.5-, 1.6-, and 1.5-fold, respectively (P < 0.05). In the ischemic hindlimb model, injection of diabetic BM-MNCs isolated from NAC-treated or gp91(phox)-deficient diabetic mice increased neovascularization by approximately 1.5-fold greater than untreated diabetic BM-MNCs (P < 0.05). Thus, inhibition of NADPH oxidase-derived ROS overproduction improves the angiogenic and vasculogenic processes and restores postischemic neovascularization in type 1 diabetic mice. de la Chapelle, 75475 Paris Cedex 10, France. |
NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.
Targets by SciMiner Summary
| HUGO ID | Symbol | Target Name | #Occur | ActualStr |
|---|---|---|---|---|
| 12680 | VEGFA | vascular endothelial growth factor A | 38 | VEGF | vascular endothelial growth factor a | vegf a | VEGF-A | VEGF-A-induced | |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | 30 | gp91 phox | |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | 23 | nadph oxidase | |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | 18 | Rac-1 | Rac1 | |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | 7 | p67 phox | |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | 7 | p47 | |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | 2 | tumor necrosis factor | |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | 2 | p22 phox | |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | 1 | endothelial nitric oxide synthase | |
| 12724 | VTN | vitronectin | 1 | vitronectin | |
| 6876 | MAPK14 | mitogen-activated protein kinase 14 | 1 | p38 mitogen activated protein kinase | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | Rac1 | 1.5 | or with in vivo electrotransfer of a plasmid encoding dominant-negative Rac1 (50 50 _amp_#x003bc g for 21 days |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | Rac1 | 1.5 | generation by gp91 phox deficiency or by administration of dominant-negative Rac1 |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | Rac1 | 1.5 | electrotransfer of a pCAG expression plasmid encoding for dominant-negative mutant Rac1 (N17Rac1, N17Rac1 50 _amp_#x003bc g injected in the gastrocnemius muscle |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF-A | 7.3 | To further analyze the role of VEGF-A up-regulation in NAC-induced restoration of neovascularization NAC-treated diabetic mice also |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 5.3 | also received an intraperitoneal injection of neutralizing antibody directed against VEGF receptor 2 (anti-Flk-1, anti-Flk-1 100 _amp_#x003bc;g/day, _amp_#x003bc g day clone |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF-A | 7.3 | Antibodies against VEGF-A (1:2000, 1 2000 Santa Cruz Biotechnology Santa Cruz CA gp91 |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.6 | gp91 phox (1:500, 1 500 BD Transduction Franklin Lakes NJ p47 phox (1:2000, 1 2000 BD Transduction p67 phox (1:2000, 1 |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | Rac1 | 1.5 | 2000 BD Transduction p67 phox (1:2000, 1 2000 BD Transduction Rac1 (1:1000, 1 1000 Cell Signaling Danvers MA phospho-p38 mitogen-activated protein |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | Rac-1 | 0.5 | Treatment with NAC and dominant-negative Rac-1 or gp91 phox deficiency abrogated ischemia- and diabetes-induced increases in |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.6 | controls ( P _amp_#x0003c 0.01 and P _amp_#x0003c 0.05 respectively p47 phox and Rac1 protein levels also tended to be increased |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | Rac1 | 1.5 | _amp_#x0003c 0.01 and P _amp_#x0003c 0.05 respectively p47 phox and Rac1 protein levels also tended to be increased but this did |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | Rac1 | 1.5 | In diabetic mice gp91 phox and Rac1 protein levels were further increased by 1.4- and 1.3-fold in |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.6 | In contrast p47 phox and p67 phox protein content was decreased in diabetic |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | Rac1 | 1.5 | together these results indicate an up-regulation of gp91 phox and Rac1 protein content and increased ROS levels in diabetic ischemic muscles |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | Rac1 | 1.5 | ROS generation by gp91 phox deficiency or administration of dominant-negative Rac1 restored postischemic neovascularization in diabetic animals to control levels (Figure |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF-A | 7.3 | Results NADPH Oxidase Inhibition Restored VEGF-A Protein Expression in Diabetic Mice We sought to determine the |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF-A | 7.3 | VEGF-A signaling represents a critical rate-limiting step in both physiological and |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF-A | 7.3 | In control mice VEGF-A protein levels were decreased by 25% in NAC-treated animals and |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF-A | 7.3 | In diabetic mice VEGF-A levels were reduced by 60% in ischemic tissues compared to |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF-A | 7.3 | Interestingly VEGF-A protein contents were significantly increased by 2.5- 2.0- and 2.7-fold |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | Rac1 | 1.5 | and 2.7-fold in diabetic animals treated with NAC or dominant-negative Rac1 and in gp91 phox -deficient diabetic mice respectively compared to |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF-A | 7.3 | In addition co-treatment with anti-Flk-1 abrogated NAC-related effects suggesting that VEGF-A up-regulation participates in the restoration of vessel growth in NAC-treated |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF-A | 7.3 | of diabetes restores key pathways involved in angiogenesis such as VEGF-A signaling and postnatal vasculogenesis |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF-A | 7.3 | this effect of ROS is likely associated with impairment in VEGF-A signaling and the ability of BM-MNCs to differentiate into EPCs |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | Rac1 | 1.5 | diabetes in association with the up-regulation of gp91 phox and Rac1 expression |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.6 | However down-regulation of p47 phox and p67 phox is puzzling and does not fit |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.6 | One may speculate that the time course of ischemia-induced p47 phox and p67 phox protein regulation may differ from that |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | Rac-1 | 0.5 | regulation may differ from that observed for gp91 phox or Rac-1 |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.6 | Alternatively the down-regulation of p67 phox and p47 phox may counterbalance the rise in gp91 phox and Rac-1 |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | Rac-1 | 0.5 | p47 phox may counterbalance the rise in gp91 phox and Rac-1 protein levels and limit ROS overproduction in diabetic tissue |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF-A | 7.3 | related to an up-regulation of major proangiogenic factors such as VEGF-A 3 19 26 We also demonstrated that diabetes-induced increases in |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF-A | 7.3 | act as intracellular second messengers modulating proangiogenic pathways such as VEGF-A signaling and postnatal vasculogenesis |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | Rac-1 | 0.5 | growth 7 8 28 29 Nevertheless because gp91 phox and Rac-1 may have multiple roles in nonphagocytic cells one cannot exclude |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | Rac-1 | 0.5 | cells one cannot exclude the possibility that gp91 phox and Rac-1 may modulate neovascularization through ROS-independent related pathways |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF-A | 7.3 | 4 Representative Western blot ( a and quantitative evaluation of VEGF-A protein levels in ischemic and nonischemic tissues ( b 21 |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF-A | 7.3 | diabetes including a reduction in vascular endothelial growth factor-A (VEGF-A) VEGF-A signaling changes in inflammation-related pathways 1 2 and accumulation of |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.6 | Nox 2 and p22 phox as well as cytosolic components p47 phox and p67 phox |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 0.0 | of two subunits gp91 phox (or or Nox 2 and p22 phox as well as cytosolic components p47 phox and p67 |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | Rac1 | 1.5 | The small GTPase Rac1 is also necessary for full NADPH oxidase activity |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF-A | 7.3 | and proliferation in endothelial cells 12 and ROS directly modulate VEGF-A expression and vascular smooth muscle cell proliferation 13 Previous reports |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | Rac1 | 1.5 | suggest that both the gp91 phox -containing NADPH oxidase and Rac1 play a major role in VEGF-A-induced endothelial cell proliferation 14 |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF-A-induced | 5.3 | -containing NADPH oxidase and Rac1 play a major role in VEGF-A-induced endothelial cell proliferation 14 Similarly mice lacking gp91 phox displayed |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | Rac1 | 1.5 | Taken together these observations suggest that both gp91 phox and Rac1 play a significant role in NADPH oxidase-induced angiogenesis |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF-A | 7.3 | the involvement of NADPH oxidase-derived ROS in diabetes-induced alterations of VEGF-A expression and postnatal vasculogenesis |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | the response to unilateral femoral artery ligation was studied in wild type or gp91 phox deficient control or type 1 diabetic mice or in animals treated with the anti oxidant n acetyl l cysteine nac or with in vivo electrotransfer of a plasmid encoding dominant negative rac1 50 _amp_#x00 |
| 12680 | VEGFA | vascular endothelial growth factor A | vascular endothelial growth factor a | 1.0 | postischemic neovascularization was reduced in diabetic mice in association with down regulated vascular endothelial growth factor a protein levels. |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | wth factor levels and postischemic neovascularization were restored to nondiabetic levels by the scavenging of reactive oxygen species ros by nac administration or the inhibition of ros generation by gp91 phox deficiency or by administration of dominant negative rac1. |
| 12680 | VEGFA | vascular endothelial growth factor A | vascular endothelial growth factor | 1.0 | in diabetic animals vascular endothelial growth factor levels and postischemic neovascularization were restored to nondiabetic levels by the scavenging of reactive oxygen species ros by nac administration or the inhibition of ros generation by gp91 phox |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | in the ischemic hindlimb model injection of diabetic bm mncs isolated from nac treated or gp91 phox deficient diabetic mice increased neovascularization by ~1.5 fold greater than untreated diabetic bm mncs p _amp_#x0003c; 0.05 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | thus inhibition of nadph oxidase derived ros overproduction improves the angiogenic and vasculogenic processes and restores postischemic neovascularization in type 1 diabetic mice. |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | to induce diabetes c57bl/6 wild type mice and c57bl/6 gp91 phox deficient mice were injected intraperitoneally with 60 mg/kg streptozotocin in sodium citrate buffer 0.05 mol/l ph 4.5 daily for 5 days. |
| 12680 | VEGFA | vascular endothelial growth factor A | vegf a | 1.0 | to further analyze the role of vegf a up regulation in nac induced restoration of neovascularization nac treated diabetic mice also received an intraperitoneal injection of neutralizing antibody directed against vegf receptor 2 anti flk |
| 12680 | VEGFA | vascular endothelial growth factor A | vegf a | 1.0 | antibodies against vegf a 1:2000 santa cruz biotechnology santa cruz ca gp91 phox 1:500 bd transduction franklin lakes nj p47 phox 1:2000 bd transduction p67 phox 1:2000 bd transduction rac1 1:1000 cell signaling danvers ma p |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67 phox | 1.0 | antibodies against vegf a 1:2000 santa cruz biotechnology santa cruz ca gp91 phox 1:500 bd transduction franklin lakes nj p47 phox 1:2000 bd transduction p67 phox 1:2000 bd transduction rac1 1:1000 cell signaling danvers ma phospho p38 mitogen activated protein kinase p38mapk 1:1000 cell signaling and pan p38mapk 1:1000 santa cruz biotechnology were used for i |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | antibodies against vegf a 1:2000 santa cruz biotechnology santa cruz ca gp91 phox 1:500 bd transduction franklin lakes nj p47 phox 1:2000 bd transduction p67 phox 1:2000 bd transduction rac1 1:1000 cell signaling danvers ma phospho p38 mitogen activated protein kinase p38mapk 1:10 |
| 6876 | MAPK14 | mitogen-activated protein kinase 14 | p38 mitogen activated protein kinase | 1.0 | santa cruz biotechnology santa cruz ca gp91 phox 1:500 bd transduction franklin lakes nj p47 phox 1:2000 bd transduction p67 phox 1:2000 bd transduction rac1 1:1000 cell signaling danvers ma phospho p38 mitogen activated protein kinase p38mapk 1:1000 cell signaling and pan p38mapk 1:1000 santa cruz biotechnology were used for immunoblotting. |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | materials and methods proangiogenic effect of bm mncs bm mncs were obtained by flushing tibia and femur of wild type and gp91 phox deficient control and diabetic mice treated with or without nac. |
| 12724 | VTN | vitronectin | vitronectin | 1.0 | materials and methods bm mnc differentiation into epcs bm mncs 1.5 _amp_#x000d7; 10 6 per ml were plated on 11 mm cell culture dishes coated with rat plasma vitronectin sigma st quentin fallavier france and gelatin 0.1% and maintained in endothelial basal medium egm2; biowhittaker walkersville md . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tumor necrosis factor | 1.0 | materials and methods bm mnc apoptosis measurement bm mncs were incubated with tumor necrosis factor _amp_#x003b1; 10 ng/ml plus cycloheximide 10 _amp_#x003bc;mol/l or c2 ceramide 100 _amp_#x003bc;mol/l for 8 hours. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | results changes in ros levels and nadph oxidase subunit protein expression in control animals 7 days of ischemia raised 3 nitrotyrosine positive staining in hindlimb muscle figure 1a . |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | although the experiments with dpi and apocynin are suggestive we used gp91 phox deficient mice to obtain more definitive evidence and showed that ischemia induced up regulation of ros levels was abrogated in this setting figure 1b . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | taken together these results suggest that ischemia activates nadph oxidase dependent ros synthesis. |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | treatment with nac and dominant negative rac 1 or gp91 phox deficiency abrogated ischemia and diabetes induced increases in ros figure 1 a and b . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the increase in ros was associated with variations in protein levels of nadph oxidase subunits. |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67 phox | 1.0 | in control animals gp91 phox and p67 phox protein levels were up regulated by 2.9 fold and 1.7 fold respectively when compared to nonischemic controls p _amp_#x0003c; 0.01 and p _amp_#x0003c; 0.05 respectively . p47 phox and rac1 protein lev |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | in control animals gp91 phox and p67 phox protein levels were up regulated by 2.9 fold and 1.7 fold respectively when compared to nonischemic controls p _amp_#x0003c; 0.01 and p _amp_#x0003c; 0.05 respectively . p47 phox and rac |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | in diabetic mice gp91 phox and rac1 protein levels were further increased by 1.4 and 1.3 fold in diabetic ischemic hindlimbs compared to ischemic controls p _amp_#x0003c; 0.05; figure 2 . |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67 phox | 1.0 | in contrast p47 phox and p67 phox protein content was decreased in diabetic ischemic muscles in reference to ischemic control animals p _amp_#x0003c; 0.05; figure 2 . |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | taken together these results indicate an up regulation of gp91 phox and rac1 protein content and increased ros levels in diabetic ischemic muscles. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | results nadph oxidase blockade restored postischemic neovascularization in diabetic mice we next assessed the role of ros and nadph oxidase activity in postischemic vessel growth 21 days after ischemia. |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | in control animals neovascularization was impaired by nac administration or the absence of gp91 phox as revealed by the 40% decrease in angiographic scores the 43% decrease in capillary density and the 40% reduction in foot doppler perfusion scores figure 3 . |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | the scavenging of ros by nac administration or the inhibition of ros generation by gp91 phox deficiency or administration of dominant negative rac1 restored postischemic neovascularization in diabetic animals to control levels figure 3 . |
| 12680 | VEGFA | vascular endothelial growth factor A | vegf a | 1.0 | results nadph oxidase inhibition restored vegf a protein expression in diabetic mice we sought to determine the molecular and cellular pathways affected by diabetes induced oxidative stress. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | results nadph oxidase inhibition restored vegf a protein expression in diabetic mice we sought to determine the molecular and cellular pathways affected by diabetes induced oxidative stress. |
| 12680 | VEGFA | vascular endothelial growth factor A | vegf a | 1.0 | vegf a signaling represents a critical rate limiting step in both physiological and pathological angiogenesis. |
| 12680 | VEGFA | vascular endothelial growth factor A | vegf a | 1.0 | in control mice vegf a protein levels were decreased by 25% in nac treated animals and gp91 phox deficient mice compared to control mice p _amp_#x0003c; 0.05; figure 4 . |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | in control mice vegf a protein levels were decreased by 25% in nac treated animals and gp91 phox deficient mice compared to control mice p _amp_#x0003c; 0.05; figure 4 . |
| 12680 | VEGFA | vascular endothelial growth factor A | vegf a | 1.0 | in diabetic mice vegf a levels were reduced by 60% in ischemic tissues compared to ischemic control hindlimbs p _amp_#x0003c; 0.001; figure 4 . |
| 12680 | VEGFA | vascular endothelial growth factor A | vegf a | 1.0 | interestingly vegf a protein contents were significantly increased by 2.5 2.0 and 2.7 fold in diabetic animals treated with nac or dominant negative rac1 and in gp91 phox deficient diabetic mice respectively compared to |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | interestingly vegf a protein contents were significantly increased by 2.5 2.0 and 2.7 fold in diabetic animals treated with nac or dominant negative rac1 and in gp91 phox deficient diabetic mice respectively compared to untreated diabetic mice figure 4 . |
| 12680 | VEGFA | vascular endothelial growth factor A | vegf a | 1.0 | in addition co treatment with anti flk 1 abrogated nac related effects suggesting that vegf a up regulation participates in the restoration of vessel growth in nac treated diabetic mice figure 3 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | results nadph oxidase inhibition restored postnatal vasculogenesis in diabetic animals we finally evaluated the effects of diabetes induced increased ros on the ability of bm mncs to stimulate neovascularization. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | protein expression of nadph oxidase subunits was detected in control bm mncs. |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | treatment with nac or deficiency in gp91 phox reduced ros levels in both control and diabetic cells. |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | results nadph oxidase inhibition restored the proangiogenic potential of diabetic bm mncs the proangiogenic potential of bm mncs isolated from control mice treated with nac or gp91 phox deficient mice was lower than that observed with bm mncs isolated from control mice. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | results nadph oxidase inhibition restored the proangiogenic potential of diabetic bm mncs the proangiogenic potential of bm mncs isolated from control mice treated with nac or gp91 phox deficient mice was lower than that |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | similarly injection of bm mncs isolated from gp91 phox deficient diabetic mice improved the angiography score by 1.7 fold capillary numbers by 1.4 fold and foot perfusion by 1.6 fold compared to bm mncs isolated from untreated diabetic animals figure 6 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | results nadph oxidase inhibition restored bm mnc differentiation into endothelial progenitor cells in vitro we could not detect any significant difference in percentages of apoptotic cells in control and diabetic animals |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | nac treatment reduced p38mapk phosphorylation by 44% in diabetic cells. p38mapk phosphorylation was also decreased by 45% in diabetic gp91 phox deficient cells figure 8c . |
| 12680 | VEGFA | vascular endothelial growth factor A | vegf a | 1.0 | hat diabetes induced increases in ros levels impairs postischemic neovascularization and blockade of oxidative stress in the setting of diabetes restores key pathways involved in angiogenesis such as vegf a signaling and postnatal vasculogenesis. |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | ediate angiogenesis in both cultured cells and in vivo models of neovascularization. 13 14 a recent study also shows that vessel growth in ischemic hindlimbs is significantly hampered in mice lacking gp91 phox . 15 we could confirm these previous studies because we found that nac administration and gp91 phox deficiency reduced postischemic neovascularization. |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | . 15 we could confirm these previous studies because we found that nac administration and gp91 phox deficiency reduced postischemic neovascularization. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | nadph oxidase activity and ros production mediate angiogenesis in both cultured cells and in vivo models of neovascularization. 13 14 a recent study also shows that vessel growth in ischemic hindlimbs is significa |
| 12680 | VEGFA | vascular endothelial growth factor A | vegf a | 1.0 | we could extend those observations showing that this effect of ros is likely associated with impairment in vegf a signaling and the ability of bm mncs to differentiate into epcs. |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | we found that ros levels were higher in diabetes in association with the up regulation of gp91 phox and rac1 expression. |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67 phox | 1.0 | however down regulation of p47 phox and p67 phox is puzzling and does not fit with the increase in ros levels in ischemic diabetic tissue. |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67 phox | 1.0 | one may speculate that the time course of ischemia induced p47 phox and p67 phox protein regulation may differ from that observed for gp91 phox or rac 1. |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | one may speculate that the time course of ischemia induced p47 phox and p67 phox protein regulation may differ from that observed for gp91 phox or rac 1. |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67 phox | 1.0 | alternatively the down regulation of p67 phox and p47 phox may counterbalance the rise in gp91 phox and rac 1 protein levels and limit ros overproduction in diabetic tissue. |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | alternatively the down regulation of p67 phox and p47 phox may counterbalance the rise in gp91 phox and rac 1 protein levels and limit ros overproduction in diabetic tissue. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | nevertheless previous studies show evidence that nadph oxidase activity and expression are significantly increased in diabetic tissue. 16 18 antioxidant defense capacity is reduced in animal models of diabetes and this can also contribute to diabetes induced oxi |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | ed in diabetic tissue. 16 18 antioxidant defense capacity is reduced in animal models of diabetes and this can also contribute to diabetes induced oxidative stress. 25 we showed here that blockade of nadph oxidase activity or the scavenging of ros restores postischemic neovascularization in diabetes. |
| 12680 | VEGFA | vascular endothelial growth factor A | vegf a | 1.0 | this effect is related to an up regulation of major proangiogenic factors such as vegf a. 3 19 26 we also demonstrated that diabetes induced increases in ros enhanced p38mapk phosphorylation in bm mncs reduced bm mnc differentiation into epcs in vitro and impaired their proangiogenic pot |
| 12680 | VEGFA | vascular endothelial growth factor A | vegf a | 1.0 | in low amounts under physiological conditions ros can act as intracellular second messengers modulating proangiogenic pathways such as vegf a signaling and postnatal vasculogenesis. |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | conversely higher amounts of ros can bear negatively on vessel growth. 7 8 28 29 nevertheless because gp91 phox and rac 1 may have multiple roles in nonphagocytic cells one cannot exclude the possibility that gp91 phox and rac 1 may modulate neovascularization through ros independent related pathways. |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | and rac 1 may have multiple roles in nonphagocytic cells one cannot exclude the possibility that gp91 phox and rac 1 may modulate neovascularization through ros independent related pathways. |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | endothelial nitric oxide synthase | 1.0 | with nac improved or normalized endothelium dependent responses. 31 alternatively increased superoxide production by nadph oxidase likely reduces no bioactivity by scavenging or through uncoupling of endothelial nitric oxide synthase and may also lead to the formation of other signaling species such as peroxynitrite. 16 18 in keeping with this we found increased 3 nitrotyrosine staining in ischemic muscles consistent with increas |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in diabetic endothelial dysfunction. 30 the chronic treatment of diabetic animals with nac improved or normalized endothelium dependent responses. 31 alternatively increased superoxide production by nadph oxidase likely reduces no bioactivity by scavenging or through uncoupling of endothelial nitric oxide synthase and may also lead to the formation of other signaling species such as peroxynitrite. 16 18 in ke |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in conclusion this study reports for the first time that diabetes induced increases in nadph oxidase derived ros reduces postischemic neovascularization through the inhibition of proangiogenic pathways and impaired postnatal vasculogenesis. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | figure 2 representative western blot and quantitative evaluation of nadph oxidase subunit protein levels in ischemic and nonischemic tissues from control cont and diabetic diab animals expressed as mean _amp_#x000b1; sem n _amp_#x0003d; 6 per group. _amp_#x0002a; p _amp_#x0003c; m |
| 12680 | VEGFA | vascular endothelial growth factor A | vegf a | 1.0 | figure 4 representative western blot a and quantitative evaluation of vegf a protein levels in ischemic and nonischemic tissues b 21 days after ischemia. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | figure 5 representative western blot a and quantitative evaluation b of nadph oxidase subunit protein levels in control and diabetic bm mncs. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tumor necrosis factor | 1.0 | figure 7 a: quantification top and representative photomicrographs bottom of control and diabetic bm mnc apoptosis after incubation with tumor necrosis factor _amp_#x003b1; 10 ng/ml plus cyclohexamide chx or c2 ceramide for 8 hours. |
| 12680 | VEGFA | vascular endothelial growth factor A | vegf a | 1.0 | ndeed there are a number of equally tenable hypotheses regarding the mechanisms underlying alterations in blood vessel growth in diabetes including a reduction in vascular endothelial growth factor a vegf a signaling changes in inflammation related pathways 1 2 and accumulation of advanced glycation end products. 3 postnatal vasculogenesis can also be affected because the proangiogenic effects of bone m |
| 12680 | VEGFA | vascular endothelial growth factor A | vascular endothelial growth factor a | 1.0 | indeed there are a number of equally tenable hypotheses regarding the mechanisms underlying alterations in blood vessel growth in diabetes including a reduction in vascular endothelial growth factor a vegf a signaling changes in inflammation related pathways 1 2 and accumulation of advanced glycation end products. 3 postnatal vasculogenesis can also be affected because the proangiogenic effects of |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 phox | 1.0 | ociated nadph oxidases. 7 8 10 the nadph oxidase as found in neutrophils and endothelial cells 7 8 11 consists of a membrane localized cytochrome b558 comprised of two subunits gp91 phox or nox 2 and p22 phox as well as cytosolic components p47 phox and p67 phox . |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67 phox | 1.0 | und in neutrophils and endothelial cells 7 8 11 consists of a membrane localized cytochrome b558 comprised of two subunits gp91 phox or nox 2 and p22 phox as well as cytosolic components p47 phox and p67 phox . |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | family of membrane associated nadph oxidases. 7 8 10 the nadph oxidase as found in neutrophils and endothelial cells 7 8 11 consists of a membrane localized cytochrome b558 comprised of two subunits gp91 phox or nox 2 and p22 phox as well as cytosolic components p47 phox and p67 phox . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | a predominant source of ros in the normal vessel is thought to be a family of membrane associated nadph oxidases. 7 8 10 the nadph oxidase as found in neutrophils and endothelial cells 7 8 11 consists of a membrane localized cytochrome b558 comprised of two subunits gp91 phox or nox 2 and p22 phox as well as cytosolic components p47 pho |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the small gtpase rac1 is also necessary for full nadph oxidase activity. |
| 12680 | VEGFA | vascular endothelial growth factor A | vegf a | 1.0 | h 2 o 2 stimulates cell migration and proliferation in endothelial cells 12 and ros directly modulate vegf a expression and vascular smooth muscle cell proliferation. 13 previous reports also suggest that both the gp91 phox containing nadph oxidase and rac1 play a major role in vegf a induced endothelial ce |
| 12680 | VEGFA | vascular endothelial growth factor A | vegf a | 1.0 | expression and vascular smooth muscle cell proliferation. 13 previous reports also suggest that both the gp91 phox containing nadph oxidase and rac1 play a major role in vegf a induced endothelial cell proliferation. 14 similarly mice lacking gp91 phox displayed impaired postischemic neovascularization. 15 taken together these observations suggest that both gp91 phox and ra |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | ates cell migration and proliferation in endothelial cells 12 and ros directly modulate vegf a expression and vascular smooth muscle cell proliferation. 13 previous reports also suggest that both the gp91 phox containing nadph oxidase and rac1 play a major role in vegf a induced endothelial cell proliferation. 14 similarly mice lacking gp91 phox displayed impaired postischemic neovascularization. 15 taken |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | containing nadph oxidase and rac1 play a major role in vegf a induced endothelial cell proliferation. 14 similarly mice lacking gp91 phox displayed impaired postischemic neovascularization. 15 taken together these observations suggest that both gp91 phox and rac1 play a significant role in nadph oxidase induced angiogenesis. |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | displayed impaired postischemic neovascularization. 15 taken together these observations suggest that both gp91 phox and rac1 play a significant role in nadph oxidase induced angiogenesis. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | nd proliferation in endothelial cells 12 and ros directly modulate vegf a expression and vascular smooth muscle cell proliferation. 13 previous reports also suggest that both the gp91 phox containing nadph oxidase and rac1 play a major role in vegf a induced endothelial cell proliferation. 14 similarly mice lacking gp91 phox displayed impaired postischemic neovascularization. 15 taken together these observatio |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | iferation. 14 similarly mice lacking gp91 phox displayed impaired postischemic neovascularization. 15 taken together these observations suggest that both gp91 phox and rac1 play a significant role in nadph oxidase induced angiogenesis. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | diabetes is associated with increased nadph oxidase activation leading to ros overproduction. 16 17 a link between ros and diabetes has been evidenced in experimental models of type 1 and 2 diabetes as well as in human patients with type 2 diabetes. 7 |
| 12680 | VEGFA | vascular endothelial growth factor A | vegf a | 1.0 | in particular we sought to investigate the involvement of nadph oxidase derived ros in diabetes induced alterations of vegf a expression and postnatal vasculogenesis. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in particular we sought to investigate the involvement of nadph oxidase derived ros in diabetes induced alterations of vegf a expression and postnatal vasculogenesis. |