)| PMID |
15608082 ( ) |
|---|---|
| Title | Vascular dysfunction of venous bypass conduits is mediated by reactive oxygen species in diabetes: role of endothelin-1. |
| Abstract | Diabetes is associated with increased risk for complications following coronary bypass grafting (CABG) surgery. Augmented superoxide (*O2*) production plays an important role in diabetic complications by causing vascular dysfunction. The potent vasoconstrictor endothelin-1 (ET-1) is also elevated in diabetes and following CABG; however, the effect of ET-1 on *O2* generation and/or vascular dysfunction in bypass conduits remain unknown. Accordingly, this study investigated basal and ET-1-stimulated *O2* production in bypass conduits and determined the effect of *O2* on conduit reactivity. Saphenous vein specimens were obtained from nondiabetic (n = 24) and diabetic (n = 24) patients undergoing CABG. Dihydroethidium staining and NAD(P)H oxidase activity assays (5380 +/- 940 versus 16,362 +/- 2550 relative light units/microg) demonstrated increased basal *O2* levels in the diabetes group (p < 0.05). Plasma ET-1 levels were associated with elevated basal *O2* levels, and treatment of conduits with exogenous ET-1 further increased *O2* production and augmented vasoconstriction. Furthermore, vascular relaxation was impaired in the diabetic group (75 versus 40%), which was restored by *O2* scavenger superoxide dismutase. These findings suggest that ET-1 causes bypass conduits dysfunction via stimulation of *O2* production in diabetes. Novel therapies that attenuate *O2* generation in bypass conduits may improve acute and late outcome of CABG in diabetic patients. College of Pharmacy, Augusta, GA 30912, USA. aergul@mail.mcg.edu |
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 |
|---|---|---|---|---|
| 3176 | EDN1 | endothelin 1 | 84 | ET-1 | endothelin 1 | |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | 17 | p67phox | p67 phox | |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | 16 | p47phox | |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | 6 | angiotensin ii | ang ii | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 5 | SOD | superoxide dismutase | |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | 4 | eNOS | |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | 4 | NOS | |
| 19404 | NOXO1 | NADPH oxidase organizer 1 | 3 | p41nox | NOXO1 | |
| 10668 | NOXA1 | NADPH oxidase activator 1 | 3 | p51nox | NOXA1 | |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | 3 | p22phox | |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | 2 | nitric oxide synthase | |
| 132 | ACTB | actin, beta | 2 | beta actin | beta-actin | |
| 7662 | NCF4 | neutrophil cytosolic factor 4, 40kDa | 2 | p40phox | |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | 2 | nadph oxidase | |
| 7891 | NOX4 | NADPH oxidase 4 | 2 | nox4 | NOX4 | |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | 1 | gp91phox | |
| 12805 | XDH | xanthine dehydrogenase | 1 | xanthine oxidase | |
| 6081 | INS | insulin | 1 | insulin | |
| 7889 | NOX1 | NADPH oxidase 1 | 1 | nox1 | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | The potent vasoconstrictor endothelin-1 (ET-1) ET-1 is also elevated in diabetes and following CABG however the |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | elevated in diabetes and following CABG however the effect of ET-1 on generation and/or and or vascular dysfunction in bypass conduits |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | Plasma ET-1 levels were associated with elevated basal levels and treatment of |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | with elevated basal levels and treatment of conduits with exogenous ET-1 further increased production and augmented vasoconstriction |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | These findings suggest that ET-1 causes bypass conduits dysfunction via stimulation of production in diabetes |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 1.9 | NAD(P)H NAD P H oxidase and uncoupled nitric-oxide synthase (eNOS) eNOS |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | ET-1 is a potent vasoactive peptide with mitogenic properties |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | Elevated plasma levels of ET-1 have been reported in atherosclerosis and diabetes as well as |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | CABG results in a biphasic increase in circulating ET-1 levels which is associated with a complex recovery in the |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | Higher plasma ET-1 levels are associated with longer intensive care unit stay (Dorman |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | Furthermore there is a positive correlation between conduit sensitivity to ET-1 and a prolonged need for vasodilator support with nitroglycerin (Bond |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | These observations provide evidence that increased ET-1 levels may negatively impact outcome in CABG patients |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | Yet the mechanism by which ET-1 alters bypass conduit function in diabetes remains to be determined |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | (2003 2003 found that ET-1 stimulates production via activation of NAD(P)H NAD P H oxidase |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | reactivity of bypass conduits and 2 determine the effect of ET-1 on production in CABG conduits in diabetes and identify the |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | To determine the effect of ET-1 on superoxide generation vessel segments were incubated with 10 or |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | generation vessel segments were incubated with 10 or 100 nM ET-1 for 30 min and then frozen |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | Since ET-1 is the most potent contractile agent and is also elevated |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | data on Fig 1 and Table 2 maximum response to ET-1 was significantly higher in the diabetic group (167 167 _amp_#177 |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | a significant difference in the sensitivity (EC EC 50 to ET-1 (48 48 _amp_#177 11 versus 43 _amp_#177 12 nM |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | of bypass conduits with PEG-SOD reduced the maximum contraction to ET-1 from 167 _amp_#177 9to139 _amp_#177 5% and 124 _amp_#177 7to112 |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | Major findings of this study are that ET-1 causes increased contraction as well as impaired vasorelaxation of saphenous |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | production in bypass conduits which is associated with increased plasma ET-1 levels |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | These results suggest that ET-1 mediates vascular dysfunction of saphenous vein conduits and provide important |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | ET-1 a potent vasoactive peptide has been shown to mediate vasoconstriction |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | Bond and colleagues (2001 2001 reported that circulating ET-1 levels increase during CABG surgery in a biphasic manner |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | lengthened intensive care unit stay are associated with elevated plasma ET-1 and increased bypass conduit sensitivity to ET-1 (Dorman Dorman et |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | with elevated plasma ET-1 and increased bypass conduit sensitivity to ET-1 (Dorman Dorman et al. 2000 |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | However whether and to what extent ET-1 contributes to vascular dysfunction in high-risk patients remained unknown |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | In light of the observations that increased ET-1 levels are associated with diabetic complications (Hattori Hattori et al. |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | complications (Herlitz Herlitz et al. 2000 we specifically investigated plasma ET-1 levels and ET-1-mediated graft reactivity in diabetic patients |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | Results of this study demonstrate that vasoconstrictor response to ET-1 not to PE is heightened in the saphenous vein specimens |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | we demonstrate that endothelium-dependent vasorelaxation of bypass conduits preconstricted with ET-1 is impaired in diabetic patients via excess generation of |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 1.9 | Second ONOO can oxidize tetrahydrobiopterin an important cofactor for eNOS and this will lead to decreased NO and increased superoxide |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 1.9 | will lead to decreased NO and increased superoxide formation by eNOS |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 0.9 | species generation include NAD(P)H NAD P H oxidase xanthine oxidase NOS lipooxygenases and mitochondrial respiratory chain enzymes (Guzik Guzik et al. |
| 7662 | NCF4 | neutrophil cytosolic factor 4, 40kDa | p40phox | 1.6 | Cytoplasmic subunits (p40phox, p40phox p47phox and p67phox are translocated to the membrane where they |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.4 | Cytoplasmic subunits (p40phox, p40phox p47phox and p67phox are translocated to the membrane where they associate |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 3.1 | Cytoplasmic subunits (p40phox, p40phox p47phox and p67phox are translocated to the membrane where they associate with the |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.0 | membrane where they associate with the membrane subunits p22phox and gp91phox (or or homologs nox1 and nox4 to form the active |
| 7889 | NOX1 | NADPH oxidase 1 | nox1 | 0.9 | with the membrane subunits p22phox and gp91phox (or or homologs nox1 and nox4 to form the active enzyme |
| 7891 | NOX4 | NADPH oxidase 4 | NOX4 | 0.9 | with the membrane subunits p22phox and gp91phox (or or homologs nox1 and nox4 to form the active enzyme |
| 7891 | NOX4 | NADPH oxidase 4 | nox4 | 0.9 | membrane subunits p22phox and gp91phox (or or homologs nox1 and nox4 to form the active enzyme |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 0.1 | to the membrane where they associate with the membrane subunits p22phox and gp91phox (or or homologs nox1 and nox4 to form |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.4 | There is recent evidence that novel homologues of p47phox (p41nox p41nox or NOXO1 and p67phox (p51nox p51nox or NOXA1 |
| 19404 | NOXO1 | NADPH oxidase organizer 1 | p41nox | 2.4 | There is recent evidence that novel homologues of p47phox (p41nox p41nox or NOXO1 and p67phox (p51nox p51nox or NOXA1 can substitute |
| 19404 | NOXO1 | NADPH oxidase organizer 1 | NOXO1 | 2.4 | recent evidence that novel homologues of p47phox (p41nox p41nox or NOXO1 and p67phox (p51nox p51nox or NOXA1 can substitute for p47phox |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 3.1 | that novel homologues of p47phox (p41nox p41nox or NOXO1 and p67phox (p51nox p51nox or NOXA1 can substitute for p47phox and p67 |
| 10668 | NOXA1 | NADPH oxidase activator 1 | p51nox | 2.4 | homologues of p47phox (p41nox p41nox or NOXO1 and p67phox (p51nox p51nox or NOXA1 can substitute for p47phox and p67 phox (Banfi |
| 10668 | NOXA1 | NADPH oxidase activator 1 | NOXA1 | 2.4 | p47phox (p41nox p41nox or NOXO1 and p67phox (p51nox p51nox or NOXA1 can substitute for p47phox and p67 phox (Banfi Banfi et |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.4 | NOXO1 and p67phox (p51nox p51nox or NOXA1 can substitute for p47phox and p67 phox (Banfi Banfi et al. 2003 Takeya et |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67 | 0.1 | p67phox (p51nox p51nox or NOXA1 can substitute for p47phox and p67 phox (Banfi Banfi et al. 2003 Takeya et al. 2003 |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | We also found that plasma ET-1 levels are significantly higher in the diabetic patients and this |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | One possible explanation is that elevated ET-1 levels might have already stimulated downstream targets of ROS production |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | with modulation of ET-1-mediated vascular reactivity by and elevated plasma ET-1 levels in diabetic patients undergoing CABG we asked whether ET-1 |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | ET-1 levels in diabetic patients undergoing CABG we asked whether ET-1 stimulates ROS generation in graft conduits and identify the mechanisms |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | DHE staining of SV specimens stimulated with ET-1 demonstrated increased production in both patient groups which was more |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | (2003 2003 demonstrated that ET-1 increases vascular generation via NAD(P)H NAD P H oxidase |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | (2000, 2000 2002 and Li (2003), 2003 we hypothesized that ET-1 induces production by promoting the translocation of p47phox and p67phox |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.4 | hypothesized that ET-1 induces production by promoting the translocation of p47phox and p67phox cytoplasmic subunits of NAD(P)H NAD P H oxidase |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 3.1 | ET-1 induces production by promoting the translocation of p47phox and p67phox cytoplasmic subunits of NAD(P)H NAD P H oxidase to the |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | hypothesis we measured oxidase activity in SV specimens stimulated with ET-1 as well as determining the protein levels of p47phox and |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.4 | with ET-1 as well as determining the protein levels of p47phox and p67phox in cytoplasmic and membrane fractions prepared from bypass |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 3.1 | as well as determining the protein levels of p47phox and p67phox in cytoplasmic and membrane fractions prepared from bypass conduits stimulated |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | cytoplasmic and membrane fractions prepared from bypass conduits stimulated with ET-1 |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | ET-1 stimulation also failed to cause a shift of p47phox and |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.4 | ET-1 stimulation also failed to cause a shift of p47phox and p67phox from the cytoplasm to membrane |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 3.1 | stimulation also failed to cause a shift of p47phox and p67phox from the cytoplasm to membrane |
| 19404 | NOXO1 | NADPH oxidase organizer 1 | NOXO1 | 2.4 | In light of the recent evidence that NOXO1 and NOXA1 can substitute for p47phox and p67phox respectively one |
| 10668 | NOXA1 | NADPH oxidase activator 1 | NOXA1 | 2.4 | In light of the recent evidence that NOXO1 and NOXA1 can substitute for p47phox and p67phox respectively one possibility is |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.4 | the recent evidence that NOXO1 and NOXA1 can substitute for p47phox and p67phox respectively one possibility is that ET-1 may stimulate |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 3.1 | evidence that NOXO1 and NOXA1 can substitute for p47phox and p67phox respectively one possibility is that ET-1 may stimulate these novel |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | substitute for p47phox and p67phox respectively one possibility is that ET-1 may stimulate these novel homologues and not conventional cytoplasmic subunits |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | (2004 2004 reported that Ang II and ET-1 regulate mitogen-activated protein kinases through different redox-dependent pathways in human |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | Although Ang II induces NAD(P)H NAD P H oxidase-mediated ROS ET-1 predominantly stimulates the generation of mitochondrial-derived superoxide suggesting that mechanisms |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | Nevertheless the findings of this study demonstrate that ET-1 alters bypass conduit reactivity in part by stimulating excess formation |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | This study also provides novel evidence that ET-1 induces via a non-NAD(P)H non-NAD P H dependent mechanism in |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | Cumulative dose-response curves to ET-1 in saphenous vein bypass conduits obtained from diabetic and nondiabetic |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | Vasoconstrictor response to ET-1 is increased in diabetic patients ( n = 15 and |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | conduits obtained from diabetic and nondiabetic patients with or without ET-1 stimulation and image analysis of all cases (B) B ( |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | Fluorescent intensity is markedly increased in all layers by ET-1 stimulation and this effect is more prominent in the diabetes |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | diabetes group PEG-SOD denotes serial DHE-stained sections incubated with PEG-conjugated SOD (150 150 U/ml) U ml * p _lt_ 0.001 diabetic |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | ml * p _lt_ 0.001 diabetic versus nondiabetic or diabetic ET-1 |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 0.9 | the absence and presence of oxidase inhibitors apocynin and DPI NOS inhibitor N -nitro-L -arginine and superoxide scavengers tiron and PEG-SOD |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | B effect of ET-1 on conduit production |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | Vessels were treated with ET-1 (100 100 nM for 30 min and then homogenized |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | Plasma ET-1 levels were significantly higher in diabetic CABG patients compared with |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | Linear regression analysis of plasma ET-1 and basal NAD(P)H NAD P H activity shown in Fig |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.4 | A representative immunoblot of cytoplasmic subunits p47phox and p67phox in bypass conduits stimulated with ET-1 |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 3.1 | A representative immunoblot of cytoplasmic subunits p47phox and p67phox in bypass conduits stimulated with ET-1 |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | cytoplasmic subunits p47phox and p67phox in bypass conduits stimulated with ET-1 |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.4 | separated on SDS-polyacrylamide gel electrophoresis and blotted with antibodies against p47phox or p67phox |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 3.1 | SDS-polyacrylamide gel electrophoresis and blotted with antibodies against p47phox or p67phox |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.4 | of all the specimens ( n = 4 analyzed for p47phox protein expression are summarized in panel B |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | vessels the dose-response curves were generated using progressive concentrations of ET-1 (1-200 1-200 nM and the contractile response obtained with each |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | nM and the contractile response obtained with each concentration of ET-1 were expressed as percentage of tension generated by 70 mM |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | min after the equilibration step and the dose-response curve to ET-1 was generated in the presence of PEG-SOD |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | To determine whether the augmented contractility is specific for ET-1 in a subset of patients ( n = 6 contractile |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | at least 30 min rings were precontracted with 10 nM ET-1 for 30 min followed by a dose-response curve for ACh |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | Similar to ET-1 dose-response curve experiments vasorelaxation experiments were performed in the presence |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | The specificity of L-012 for was confirmed by addition of SOD (150 150 U/ml), U ml which decreased the luminescence to |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | Measurement of ET-1 |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | The amount of ET-1 in the plasma was determined using an enzyme-linked immunoassay kit |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | enzyme-linked immunoassay kit specifically designed for direct measurement of plasma ET-1 (American American Research Products Belmont MA as we previously described |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.4 | membrane translocation of cytoplasmic NAD(P)H NAD P H oxidase subunits p47phox and p67phox (Santa Santa Cruz Biotechnology Inc. Santa Cruz CA |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 3.1 | of cytoplasmic NAD(P)H NAD P H oxidase subunits p47phox and p67phox (Santa Santa Cruz Biotechnology Inc. Santa Cruz CA were determined |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.4 | by incubation with the primary antibodies for 24 h for p47phox and 48 h for p67phox |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 3.1 | antibodies for 24 h for p47phox and 48 h for p67phox |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.4 | IgG from Santa Cruz Biotechnology Inc. the bands corresponding to p47phox or p67phox were visualized using the Supersignal West Pico chemiluminescent |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 3.1 | Santa Cruz Biotechnology Inc. the bands corresponding to p47phox or p67phox were visualized using the Supersignal West Pico chemiluminescent substrate development |
| 132 | ACTB | actin, beta | beta-actin | 0.3 | protein loading in each gel was verified by immunoblotting for beta-actin |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | reactivity experiments showing that augments ET-1-mediated vasoconstriction the effect of ET-1 on production was also investigated |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | Vascular rings were stimulated with 100 nM ET-1 for 30 min which caused a significant increase in formation |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | Lower concentrations of ET-1 (10 10 nM also increased DHE fluorescence by 27% in |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | To determine the effect of ET-1 on NAD(P)H NAD P H oxidase activity SV samples ( |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | n = 5/group) 5 group were incubated with 100 nM ET-1 for 30 min and oxidase activity was then measured |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | As shown in Fig 4B ET-1 had no effect on membrane NAD(P)H NAD P H oxidase |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | ET-1 stimulation did not alter the low cytosolic oxidase activity in |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | Plasma ET-1 Levels |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | Systemic ET-1 levels in the preoperative period were significantly higher in the |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | To examine the relationship between ET-1 levels and basal superoxide production linear regression analysis was performed |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | A positive linear relationship was observed between plasma ET-1 and NAD(P)H NAD P H activity with r = 0.72 |
| 7662 | NCF4 | neutrophil cytosolic factor 4, 40kDa | p40phox | 1.6 | homologs in vascular smooth muscle cells and 3 cytosolic subunits p40phox p47phox and p67phox which are translocated to the membrane upon |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.4 | in vascular smooth muscle cells and 3 cytosolic subunits p40phox p47phox and p67phox which are translocated to the membrane upon activation |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 3.1 | smooth muscle cells and 3 cytosolic subunits p40phox p47phox and p67phox which are translocated to the membrane upon activation |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 0.0 | NAD(P)H NAD P H oxidase consists of two membrane p22phox and p91phox (nox-1 nox-1 or nox-4 homologs in vascular smooth |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.4 | Therefore tissue levels of p47phox and p67phox subunits were assayed in the cytosolic and pellet |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 3.1 | Therefore tissue levels of p47phox and p67phox subunits were assayed in the cytosolic and pellet (membrane) membrane |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | the cytosolic and pellet (membrane) membrane fractions to determine whether ET-1 promotes translocation of these subunits and thereby activation of NAD(P)H |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 2.4 | The p47phox subunit was detected primarily in the cytosolic fraction and protein |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | ET-1 stimulation increased protein levels in the cytosolic fraction but did |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 3.1 | Bands corresponding to p67phox subunit were detected in the cytosolic fractions but higher molecular |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 3.1 | molecular weight bands around 90 kDa (possibly possibly p22phox and p67phox complex were also found in the membrane fractions |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 0.1 | but higher molecular weight bands around 90 kDa (possibly possibly p22phox and p67phox complex were also found in the membrane fractions |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | Furthermore ET-1 stimulation (100 100 nM for 30 min did not affect |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 0.9 | ROS reactive oxygen species NO nitric oxide superoxide ONOO peroxynitrite NOS nitric-oxide synthase eNOS endothelial NOS ET-1 endothelin-1 SV saphenous vein |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 1.9 | species NO nitric oxide superoxide ONOO peroxynitrite NOS nitric-oxide synthase eNOS endothelial NOS ET-1 endothelin-1 SV saphenous vein ACh acetylcholine PEG-SOD |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 0.9 | nitric oxide superoxide ONOO peroxynitrite NOS nitric-oxide synthase eNOS endothelial NOS ET-1 endothelin-1 SV saphenous vein ACh acetylcholine PEG-SOD polyethylene glycol-conjugated |
| 3176 | EDN1 | endothelin 1 | ET-1 | 0.3 | oxide superoxide ONOO peroxynitrite NOS nitric-oxide synthase eNOS endothelial NOS ET-1 endothelin-1 SV saphenous vein ACh acetylcholine PEG-SOD polyethylene glycol-conjugated superoxide |
| 3176 | EDN1 | endothelin 1 | endothelin 1 | 1.0 | the potent vasoconstrictor endothelin 1 et 1 is also elevated in diabetes and following cabg; however the effect of et 1 on generation and/or vascular dysfunction in bypass conduits remain unknown. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | furthermore vascular relaxation was impaired in the diabetic group 75 versus 40% which was restored by scavenger superoxide dismutase. |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | nitric oxide synthase | 1.0 | 2000 2002 demonstrated that enhanced generation in bypass conduits of diabetic patients is mediated by nad p h oxidase and uncoupled nitric oxide synthase enos . |
| 6081 | INS | insulin | insulin | 1.0 | another group recently reported that vasodilator responses to k channel openers are reduced in two experimental models of insulin resistance and increased production is responsible for impaired relaxation erdos et al. 2004 . |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | vascular sources that augment reactive species generation include nad p h oxidase xanthine oxidase nos lipooxygenases and mitochondrial respiratory chain enzymes guzik et al. 2000 2002 ; brownlee 2001 ; aliciguzel et al. 2003 . |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67 phox | 1.0 | there is recent evidence that novel homologues of p47phox p41nox or noxo1 and p67phox p51nox or noxa1 can substitute for p47phox and p67 phox banfi et al. 2003 ; takeya et al. 2003 ; griendling 2004 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | apocynin inhibits generation by blocking the subunit association of nadph oxidase but if the subunit complex is already formed it does not inhibit free radical formation. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | et 1 induces production by promoting the translocation of p47phox and p67phox cytoplasmic subunits of nad p h oxidase to the membrane compartment and activating the oxidase as seen by angiotensin ii ang ii stimulation touyz et al. 2002 . |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | angiotensin ii | 1.0 | pothesized that et 1 induces production by promoting the translocation of p47phox and p67phox cytoplasmic subunits of nad p h oxidase to the membrane compartment and activating the oxidase as seen by angiotensin ii ang ii stimulation touyz et al. 2002 . |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | 2004 reported that ang ii and et 1 regulate mitogen activated protein kinases through different redox dependent pathways in human vascular smooth muscle cells. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | although ang ii induces nad p h oxidase mediated ros et 1 predominantly stimulates the generation of mitochondrial derived superoxide suggesting that mechanisms of et 1 mediated production might be different in huma |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | to determine the role of in modulating the contractile response additional rings were incubated with 150 u/ml polyethylene glycol conjugated superoxide dismutase peg sod for 30 min after the equilibration step and the dose response curve to et 1 was generated in the presence of peg sod. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | nadph oxidase activity. |
| 132 | ACTB | actin, beta | beta actin | 1.0 | equal protein loading in each gel was verified by immunoblotting for beta actin. |
| 3176 | EDN1 | endothelin 1 | endothelin 1 | 1.0 | abbreviations: cabg coronary artery bypass grafting; ros reactive oxygen species; no nitric oxide; superoxide; onoo peroxynitrite; nos nitric oxide synthase; enos endothelial nos; et 1 endothelin 1; sv saphenous vein; ach acetylcholine; peg sod polyethylene glycol conjugated superoxide dismutase; pe phenylephrine; l 012 8 amino 5 chloro 7 phenylpyrido[3 4 d ]pyridazine 1 4 2 h 3 h dione; rlu/mi |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | hydroethidium; dpi diphenyleneiodonium; bq 123 cyclo l leu d trp d asp l pro d val ; bq 788 n [ cis 2 6 dimethyl 1 piperidinyl carbonyl] 4 methyl l leucyl 1 methoxycarbonyl d tryptophyl d norleucine; ang ii angiotensin ii. |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | nitric oxide synthase | 1.0 | abbreviations: cabg coronary artery bypass grafting; ros reactive oxygen species; no nitric oxide; superoxide; onoo peroxynitrite; nos nitric oxide synthase; enos endothelial nos; et 1 endothelin 1; sv saphenous vein; ach acetylcholine; peg sod polyethylene glycol conjugated superoxide dismutase; pe phenylephrine; l 012 8 amino 5 chloro 7 phenylpyrido[3 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | cies; no nitric oxide; superoxide; onoo peroxynitrite; nos nitric oxide synthase; enos endothelial nos; et 1 endothelin 1; sv saphenous vein; ach acetylcholine; peg sod polyethylene glycol conjugated superoxide dismutase; pe phenylephrine; l 012 8 amino 5 chloro 7 phenylpyrido[3 4 d ]pyridazine 1 4 2 h 3 h dione; rlu/min _amp_#183; microg relative light units per minute per micrograms of protein; dhe dihydroethidium; |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | angiotensin ii | 1.0 | hidium; dpi diphenyleneiodonium; bq 123 cyclo l leu d trp d asp l pro d val ; bq 788 n [ cis 2 6 dimethyl 1 piperidinyl carbonyl] 4 methyl l leucyl 1 methoxycarbonyl d tryptophyl d norleucine; ang ii angiotensin ii. |
| 3176 | EDN1 | endothelin 1 | endothelin 1 | 1.0 | endothelin 1|fluorescent dyes|reactive oxygen species|dihydroethidium|ethidium|nadph oxidase| |