)| PMID |
16741160 ( ) |
|---|---|
| Title | Tumor necrosis factor-alpha induces endothelial dysfunction in the prediabetic metabolic syndrome. |
| Abstract | Inflammation is a condition that underscores many cardiovascular pathologies including endothelial dysfunction, but no link is yet established between the vascular pathology of the metabolic syndrome with a particular inflammatory cytokine. We hypothesized that impairments in coronary endothelial function in the obese condition the prediabetic metabolic syndrome is caused by TNF-alpha overexpression. To test this, we measured endothelium-dependent (acetylcholine) and -independent vasodilation (sodium nitroprusside) of isolated, pressurized coronary small arteries from lean control and Zucker obese fatty (ZOF, a model of prediabetic metabolic syndrome) rats. In ZOF rats, dilation to ACh was blunted compared with lean rats, but sodium nitroprusside-induced dilation was comparable. Superoxide (O2*-) generation was elevated in vessels from ZOF rats compared with lean rats, and administration of the O2*- scavenger TEMPOL, NAD(P)H oxidase inhibitor (apocynin), or anti-TNF-alpha restored endothelium-dependent dilation in the ZOF rats. Real-time PCR and Western blotting revealed that mRNA and protein of TNF-alpha were higher in ZOF rats than that in lean rats, whereas eNOS protein levels were reduced in the ZOF versus lean rats. Immunostaining showed that TNF-alpha in ZOF rat heart is localized in endothelial cells and vascular smooth muscle cells. Expression of NAD(P)H subunits p22 and p40-phox were elevated in ZOF compared with lean animals. Administration of TNF-alpha more than 3 days also induced expression of these NAD(P)H subunits and abrogated endothelium-dependent dilation. In conclusion, the results demonstrate the endothelial dysfunction occurring in the metabolic syndrome is the result of effects of the inflammatory cytokine TNF-alpha and subsequent production of O2*-. Center, New Orleans, USA. |
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 |
|---|---|---|---|---|
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | 244 | tumor necrosis factor | TNF-alpha-induced | TNF-alpha-Induced | tnf alpha | |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | 24 | eNOS | |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | 16 | p22 phox | p22-phox | |
| 12805 | XDH | xanthine dehydrogenase | 7 | xanthine oxidase | |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | 6 | p67 phox | p67-phox | |
| 6081 | INS | insulin | 5 | insulin | |
| 12726 | VWF | von Willebrand factor | 5 | von willebrand factor | vWF | |
| 1693 | CD68 | CD68 molecule | 4 | CD68 | |
| 129 | ACTA1 | actin, alpha 1, skeletal muscle | 4 | alpha-actin | alpha actin | |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | 4 | NOS | |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | 3 | IL-6 | il 6 | interleukin 6 | |
| 2367 | CRP | C-reactive protein, pentraxin-related | 2 | CRP | c reactive protein | |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | 2 | gp-91-phox | |
| 7097 | MIF | macrophage migration inhibitory factor (glycosylation-inhibiting factor) | 1 | MIF | |
| 195 | ADAM17 | ADAM metallopeptidase domain 17 (tumor necrosis factor, alpha, converting enzyme) | 1 | tnf alpha converting enzyme | |
| 6554 | LEPR | leptin receptor | 1 | leptin receptor | |
| 143 | ACTC1 | actin, alpha, cardiac muscle 1 | 1 | smooth muscle actin | |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | 1 | p47 | |
| 4141 | GAPDH | glyceraldehyde-3-phosphate dehydrogenase | 1 | GAPDH | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 1 | superoxide dismutase | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | the obese condition the prediabetic metabolic syndrome is caused by TNF-alpha overexpression |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | PCR and Western blotting revealed that mRNA and protein of TNF-alpha were higher in ZOF rats than that in lean rats |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 7.0 | higher in ZOF rats than that in lean rats whereas eNOS protein levels were reduced in the ZOF versus lean rats |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Immunostaining showed that TNF-alpha in ZOF rat heart is localized in endothelial cells and |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 0.0 | Expression of NAD(P)H NAD P H subunits p22 and p40-phox were elevated in ZOF compared with lean animals |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Administration of TNF-alpha more than 3 days also induced expression of these NAD(P)H |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | syndrome is the result of effects of the inflammatory cytokine TNF-alpha and subsequent production of O 2 _amp_#183 |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF | 4.4 | Tumor necrosis factor TNF -alpha a proinflammatory cytokine originally defined by its antitumor activity |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Therefore we proposed that TNF-alpha may be the inflammatory basis leading from the metabolic syndrome |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | evaluated the endothelium-dependent and -independent vasodilation the circulating levels of TNF-alpha and its expression at the wall of coronary small arteries |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | We also tested the mechanisms by which TNF-alpha induces endothelial dysfunction and the role of O 2 _amp_#183 |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Determination of Plasma TNF-alpha |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Plasma TNF-alpha was measured using BIO-Plex mouse 3-plex assay (Bio-Rad Bio-Rad Laboratories |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | were added to the microplate to assess the level of TNF-alpha in plasma |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | TNF-alpha concentrations (picograms picograms per milliliter were automatically calculated by BIO-Plex |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Treatment With TNF-alpha Apocynin and TNF-alpha Neutralization |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Treatment With TNF-alpha Apocynin and TNF-alpha Neutralization |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | We administered TNF-alpha (10 10 microg/kg, microg kg IP R_amp_D Systems to lean |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Systems to lean rats for 3 days to determine whether TNF-alpha can inhibit coronary arterial dilations mediated by NO |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | We also tested whether TNF-alpha affected mRNA expression of NAD(P)H NAD P H in lean |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | rats and test whether apocynin affected the protein expression of TNF-alpha and eNOS |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 7.0 | test whether apocynin affected the protein expression of TNF-alpha and eNOS |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | The neutralizing antibody to TNF-alpha anti-TNF-alpha used in these studies was 2E2 monoclonal antibody (2E2 |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | this dose of antibody was based on our estimates of TNF-alpha expression (in in the low nanogram or picogram range the |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha. | 1.7 | was able to neutralize 10- to 100-fold this amount of TNF-alpha. |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 1.2 | these vasodilations were examined by treating the vessels with the NOS inhibitor N -monomethyl-L -arginine ( L -NMMA (10 10 micromol/L, |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | To determine whether TNF-alpha was played a role in endothelial injury in the metabolic |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | To determine the role of TNF-alpha and O 2 _amp_#183 anion in altered vasoactive responses in |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | mRNA Expression of TNF-alpha and NAD(P)H NAD P H Oxidase Subunits by Real-Time PCR |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | The primers of TNF-alpha and NAD(P)H NAD P H oxidase subunits (p22-phox, p22-phox p40-phox |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22-phox | 1.5 | of TNF-alpha and NAD(P)H NAD P H oxidase subunits (p22-phox, p22-phox p40-phox p-47-phox p67-phox and gp-91-phox were designed (primer primer 3 |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67-phox | 1.5 | NAD(P)H NAD P H oxidase subunits (p22-phox, p22-phox p40-phox p-47-phox p67-phox and gp-91-phox were designed (primer primer 3 software and synthesized |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp-91-phox | 0.1 | P H oxidase subunits (p22-phox, p22-phox p40-phox p-47-phox p67-phox and gp-91-phox were designed (primer primer 3 software and synthesized (Qiagen) Qiagen |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | 2 method and presented as fold change of transcripts for TNF-alpha gene and NAD(P)H NAD P H oxidase gene in ZOF |
| 4141 | GAPDH | glyceraldehyde-3-phosphate dehydrogenase | GAPDH | 0.0 | NAD P H oxidase gene in ZOF rats normalized to GAPDH compared with lean control rats (defined defined as 1.0-fold |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Protein Expression of TNF-alpha and eNOS by Western Blot Analyses |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 7.0 | Protein Expression of TNF-alpha and eNOS by Western Blot Analyses |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | TNF-alpha and eNOS protein expression were detected by Western blot analysis |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 7.0 | TNF-alpha and eNOS protein expression were detected by Western blot analysis with the |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | were detected by Western blot analysis with the use of TNF-alpha primary antibodies (Santa Santa Cruz Biotechnology and eNOS primary antibody |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 7.0 | use of TNF-alpha primary antibodies (Santa Santa Cruz Biotechnology and eNOS primary antibody (Abcam) Abcam in 4 groups of lean rats |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | in Tris buffer then incubated with polyclonal goat antibody against TNF-alpha (R_amp_D R_amp_D systems and the endothelial cell marker von Willebrand |
| 129 | ACTA1 | actin, alpha 1, skeletal muscle | alpha-actin | 0.3 | marker von Willebrand factor (ab6994, ab6994 Abcam or smooth muscle alpha-actin (1A4, 1A4 Calbiochem or macrophages (mouse mouse anti rat CD68 |
| 1693 | CD68 | CD68 molecule | CD68 | 0.3 | alpha-actin (1A4, 1A4 Calbiochem or macrophages (mouse mouse anti rat CD68 Serotec and then incubated with a secondary fluorescent antibody (Alexa |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Plasma Concentration mRNA and Protein Expression of TNF-alpha |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha. | 1.7 | Figure 1 A shows elevations of plasma concentration of TNF-alpha. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Figure 1 B (real-time real-time PCR shows elevations of TNF-alpha expression |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | 1 C (Western Western blotting shows the protein expression of TNF-alpha in isolated coronary small arteries of lean control rats ZOF |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Our results suggest that overexpression of TNF-alpha induces activation of NAD(P)H NAD P H oxidase and production |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Importantly our findings support the concept that TNF-alpha plays a pivotal role in endothelial dysfunction in the metabolic |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Antibody neutralization of TNF-alpha prevented coronary endothelial dysfunction and reduced O 2 _amp_#183 generation |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 7.0 | and reduced O 2 _amp_#183 generation and protein expression of eNOS in ZOF rats |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | of anti-TNF-alpha on O 2 _amp_#183 production protein expression of TNF-alpha and eNOS and endothelial function in ZOF rats |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 7.0 | on O 2 _amp_#183 production protein expression of TNF-alpha and eNOS and endothelial function in ZOF rats |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Molecular evidence indicated that the expression of TNF-alpha (mRNA mRNA and protein and mRNA expression of NAD(P)H NAD |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22-phox | 1.5 | and mRNA expression of NAD(P)H NAD P H oxidase subunits p22-phox and p40-phox were significantly increased but protein expression of eNOS |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 7.0 | p22-phox and p40-phox were significantly increased but protein expression of eNOS was diminished in ZOF rats |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | TNF-alpha and the Metabolic Syndrome |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | TNF-alpha is overexpressed in obesity and likely mediates insulin resistance in |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | resistance in the major animal models of obesity neutralization of TNF-alpha with soluble TNF-alpha receptors results in the restoration of insulin |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | major animal models of obesity neutralization of TNF-alpha with soluble TNF-alpha receptors results in the restoration of insulin sensitivity and thereby |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | of insulin sensitivity and thereby demonstrates that the proinflammatory cytokine TNF-alpha is the mediator of insulin resistance |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Studies in human show increased TNF-alpha interleukin-6 (IL-6), IL-6 C reactive protein (CRP), CRP and migration |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | IL-6 | 1.3 | Studies in human show increased TNF-alpha interleukin-6 (IL-6), IL-6 C reactive protein (CRP), CRP and migration inhibitory factor (MIF) |
| 2367 | CRP | C-reactive protein, pentraxin-related | CRP | 0.6 | show increased TNF-alpha interleukin-6 (IL-6), IL-6 C reactive protein (CRP), CRP and migration inhibitory factor (MIF) MIF plasma levels indicating metabolic |
| 7097 | MIF | macrophage migration inhibitory factor (glycosylation-inhibiting factor) | MIF | 0.9 | C reactive protein (CRP), CRP and migration inhibitory factor (MIF) MIF plasma levels indicating metabolic syndrome is an inflammatory state |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | We found increased TNF-alpha mRNA expression (5-fold), 5-fold plasma concentration of TNF-alpha (8-fold), 8-fold |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | found increased TNF-alpha mRNA expression (5-fold), 5-fold plasma concentration of TNF-alpha (8-fold), 8-fold and protein expression of TNF-alpha (more more than |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | plasma concentration of TNF-alpha (8-fold), 8-fold and protein expression of TNF-alpha (more more than 3-fold in small coronary arteries in ZOF |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | If TNF-alpha is as we and others suspect 1 of the initiators |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Our immunostaining results show TNF-alpha in ZOF rat heart is localized in ECs and vascular |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | production in vascular endothelial cells and smooth muscle cells by TNF-alpha would limit NO bioavailability and reduce NO-dependent dilation |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Finally TNF-alpha can be stored within cells in a pre form and |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | stored within cells in a pre form and the enzyme TNF-alpha converting enzyme can rapidly increase levels of the active cytokine |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | There is no previous report on the endogenous role of TNF-alpha in this respect and it has been unclear whether TNF-alpha |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | TNF-alpha in this respect and it has been unclear whether TNF-alpha plays a direct role in endothelial dysfunction in the metabolic |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Recent evidence supports the idea that the effect of TNF-alpha is NO dependent by producing a rapid inhibitory action on |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 1.2 | by producing a rapid inhibitory action on NO synthase (NOS) NOS in the endothelium via activation of a sphingomyelinase/ceramide sphingomyelinase ceramide |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | pathway this mechanism is supposed to mediate the action of TNF-alpha thereby contributing to vascular endothelial dysfunction in coronary circulation under |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | In the present study we documented that TNF-alpha is critical for the development of endothelial dysfunction in the |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | TNF-alpha expression was significantly increased in ZOF rats anti-TNF-alpha restored NO-mediated |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Furthermore administration of anti-TNF-alpha protected endothelial dysfunction induced by TNF-alpha in isolated vessels from lean control rats confirming that the |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | vasodilation was restored in ZOF rats after the treatment with TNF-alpha antibodies for 3 days (IP), IP and 3 days treatment |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | for 3 days (IP), IP and 3 days treatment with TNF-alpha (IP) IP mimicked endothelial dysfunction in lean rats both demonstrating |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | is in agreement with those of previous studies showing that TNF-alpha can decrease the release of endothelial NO and induce impairment |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | The link between TNF-alpha overexpression and O 2 _amp_#183 production has been investigated by |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha-induced | 1.7 | _amp_#183 scavenger and polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) PEG-SOD prevented TNF-alpha-induced impairment of endothelium-dependent vasorelaxation in coronary arterioles |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | are consistent with these studies and support our hypotheses that TNF-alpha and O 2 _amp_#183 are connected in the production of |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 7.0 | Effect of eNOS on TNF-alpha-Induced Endothelial Dysfunction in the Metabolic Syndrome |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha-Induced | 1.7 | Effect of eNOS on TNF-alpha-Induced Endothelial Dysfunction in the Metabolic Syndrome |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha. | 1.7 | vascular endothelium is a major target for the actions of TNF-alpha. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | TNF-alpha can decrease the release of endothelial NO and induce impairment |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | variety of vascular beds however the signaling pathways that couple TNF-alpha stimulation to endothelial dysfunction in small coronary arteries remain to |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Zhang et al demonstrated that TNF-alpha inhibited NO-mediated endothelium-dependent vasorelaxation in coronary arterioles by activating sphingomyelinase |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | In the presence of L -NMMA TNF-alpha had no further inhibitory effect on the responses to endothelium-dependent |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | the responses to endothelium-dependent vasodilators suggesting that the effect of TNF-alpha is NO dependent |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | TNF-alpha is known to affect eNOS expression by affecting the half-life |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 7.0 | TNF-alpha is known to affect eNOS expression by affecting the half-life of its mRNA |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 7.0 | The protein expression of eNOS is significantly attenuated in isolated arteries in ZOF rats compared |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | We know that TNF-alpha impairs endothelial function by reducing NO bioavailability but little information |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | but little information is available in the literature on how TNF-alpha affects endothelial NOS (eNOS) eNOS activity in coronary arteries |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 1.2 | is available in the literature on how TNF-alpha affects endothelial NOS (eNOS) eNOS activity in coronary arteries |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 7.0 | in the literature on how TNF-alpha affects endothelial NOS (eNOS) eNOS activity in coronary arteries |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 7.0 | there appears to be an inconsistency between NO-mediated dilation and eNOS protein ie restoration of dilation when eNOS protein is still |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 7.0 | NO-mediated dilation and eNOS protein ie restoration of dilation when eNOS protein is still decreased we believe there are some factors |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 7.0 | Not all eNOS is active some is bound to caveolin and secondly some |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 7.0 | is active some is bound to caveolin and secondly some eNOS may be dysfunctional because of limitations in BH4 or other |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 7.0 | The total amount of eNOS may not reflect the total production of NO and the |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 7.0 | dilation because there may not be a simple match of eNOS protein with NO-mediated dilation |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | results support the idea that the major enzyme activated by TNF-alpha in the metabolic syndrome is NAD(P)H NAD P H oxidase |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha-induced | 1.7 | Our results indicate that the pathway for TNF-alpha-induced endothelial dysfunction is mediated by activation of NAD(P)H NAD P |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 7.0 | striking increase in endothelial O 2 _amp_#183 production mediated by eNOS uncoupling |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Our results demonstrate the production of TNF-alpha is essential in eliciting this oxidative stress |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.6 | protein expression of NAD(P)H NAD P H oxidase subunits p22 p47 and p67-phox are significantly increased in diabetic human tissue versus |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67-phox | 1.5 | of NAD(P)H NAD P H oxidase subunits p22 p47 and p67-phox are significantly increased in diabetic human tissue versus normal control |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 0.2 | the protein expression of NAD(P)H NAD P H oxidase subunits p22 p47 and p67-phox are significantly increased in diabetic human tissue |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22-phox | 1.5 | that mRNA expression of NAD(P)H NAD P H oxidase subunit p22-phox and p40-phox are increased _amp_2-fold in ZOF rats versus lean |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Most interestingly the TNF-alpha treatment also increases the mRNA expression of vascular NAD(P)H NAD |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22-phox | 1.5 | mRNA expression of vascular NAD(P)H NAD P H oxidase subunits p22-phox and p40-phox in the control animals |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Further studies are needed to determine the mechanism linking TNF-alpha receptor activation to NAD(P)H NAD P H oxidase |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | study indicates that the model of the metabolic syndrome increases TNF-alpha which stimulates endothelial generation of through activation of NAD(P)H NAD |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | of the metabolic syndrome_amp_#151 in terms of endothelial dysfunction_amp_#151 to TNF-alpha the subsequent activation of NAD(P)H NAD P H oxidase and |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Taken together these results further support our hypothesis that TNF-alpha and O 2 _amp_#183 are connected in the production of |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | In conclusion we found that TNF-alpha overexpression impairs endothelium-dependent vasodilation in coronary arterioles of rats affected |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | endothelial function can be restored toward normal by administration of TNF-alpha antibodies |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | The mechanism by which TNF-alpha affects endothelial function seems to be an increased superoxide production |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha. | 1.7 | therapeutic target for cardiovascular diseases associated with elevated levels of TNF-alpha. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | A Plasma concentration of inflammatory cytokine TNF-alpha is significantly increased in ZOF rats |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | B Real-time PCR of TNF-alpha mRNA from left ventricular coronary arteries in lean control and |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | B shows fold change of TNF-alpha mRNA expression which was significantly higher in ZOF rats than |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | C Western blotting showed the protein expression of TNF-alpha (normalized normalized to _amp_#223 -actin in isolated small coronary arteries |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Bars represent the increased expression of TNF-alpha in ZOF rats as a percentage of control |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | The protein expression of TNF-alpha was higher in coronary arteries of ZOF rats than in |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | coronary arteries of ZOF rats than in lean controls but TNF-alpha expression in anti-TNF-alpha- or apocynin-treated ZOF rats was similar to |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Dual fluorescence combining TNF-alpha with markers for macrophages (CD68), CD68 vascular smooth muscle ( |
| 1693 | CD68 | CD68 molecule | CD68 | 0.3 | Dual fluorescence combining TNF-alpha with markers for macrophages (CD68), CD68 vascular smooth muscle ( alpha-smooth muscle actin alpha-SMA or endothelial |
| 12726 | VWF | von Willebrand factor | vWF | 1.9 | muscle actin alpha-SMA or endothelial cells (von von Willebrand factor vWF using specific antibodies followed by a fluorescent-labeled secondary antibody |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | A through C Dual labeling of alpha-SMA (green) green and TNF-alpha (red) red in lean rat heart tissue |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | E through G Dual labeling of alpha-SMA (green) green and TNF-alpha (red) red in ZOF rat heart tissue |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | The insets D and H show a colocalization of TNF-alpha (red) red and alpha-SMA (green) green |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | through K Dual labeling of endothelial cells (red) red and TNF-alpha (green) green in ZOF rat heart tissues |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | The inset L shows a colocalization of TNF-alpha (green) green and vWF factor (red) red in ZOF rat |
| 12726 | VWF | von Willebrand factor | vWF | 1.9 | inset L shows a colocalization of TNF-alpha (green) green and vWF factor (red) red in ZOF rat heart tissues |
| 1693 | CD68 | CD68 molecule | CD68 | 0.3 | M through O Dual labeling of CD68 (red) red and TNF-alpha (green) green in ZOF rat heart |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | M through O Dual labeling of CD68 (red) red and TNF-alpha (green) green in ZOF rat heart tissue the arrow in |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | inset P show a specific macrophage staining and absence of TNF-alpha staining |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | The immunostaining results show that TNF-alpha in ZOF rat heart is expressed in vascular smooth muscle |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 1.2 | The NOS inhibitor L -NMMA (10 10 micromol/L, micromol L 30 minutes |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 7.0 | B Protein expression of eNOS in isolated coronary arteries of lean control ZOF ZOF rats |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 7.0 | (100 100 mg/kg mg kg per day 3 days IP eNOS protein was lower in ZOF rats than in lean rats |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 7.0 | protein was lower in ZOF rats than in lean rats eNOS expression in anti-TNF-alpha- or apocynin-treated ZOF rats was higher than |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | ACh-induced dilation was significantly blunted by 3 days treatment with TNF-alpha (10 10 microg/kg, microg kg n=5 but 3 days treatment |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | 0.625 mg/kg, mg kg n=6 protected endothelial dysfunction induced by TNF-alpha in lean control rats |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | mg/kg) mg kg restored the impaired endothelial function induced by TNF-alpha in vessels isolated from lean rats (n=5) n=5 (A) A |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | lean rats vs ZOF rats # P _lt_0.05 lean rats TNF-alpha vs lean rats TNF-alpha anti-TNF- alpha # P _lt_0.05 lean |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | rats # P _lt_0.05 lean rats TNF-alpha vs lean rats TNF-alpha anti-TNF- alpha # P _lt_0.05 lean rats TNF-alpha vs lean |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | lean rats TNF-alpha anti-TNF- alpha # P _lt_0.05 lean rats TNF-alpha vs lean rats TNF-alpha apocynin. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | alpha # P _lt_0.05 lean rats TNF-alpha vs lean rats TNF-alpha apocynin. |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22-phox | 1.5 | lean control mRNA expression for NAD(P)H NAD P H oxidase p22-phox and p40-phox is higher in ZOF rats than in lean |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | ZOF rats than in lean control rats and treatment by TNF-alpha (10 10 microg/kg, microg kg 3 days IP significantly increased |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22-phox | 1.5 | the mRNA expression of NAD(P)H NAD P H oxidase subunits p22-phox and p40-phox in lean rats |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Cellular Source of TNF-alpha Expression in the Metabolic Syndrome |
| 129 | ACTA1 | actin, alpha 1, skeletal muscle | alpha-actin | 0.3 | von Willebrand factor vascular smooth muscle cells (VSMCs) VSMCs ( alpha-actin or macrophages (mouse mouse anti-rat CD68 along with TNF-alpha to |
| 1693 | CD68 | CD68 molecule | CD68 | 0.3 | cells (VSMCs) VSMCs ( alpha-actin or macrophages (mouse mouse anti-rat CD68 along with TNF-alpha to establish the cell type expressing the |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | ( alpha-actin or macrophages (mouse mouse anti-rat CD68 along with TNF-alpha to establish the cell type expressing the TNF-alpha showed that |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | along with TNF-alpha to establish the cell type expressing the TNF-alpha showed that TNF-alpha in rat heart was localized in endothelial |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | to establish the cell type expressing the TNF-alpha showed that TNF-alpha in rat heart was localized in endothelial cells and vascular |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 7.0 | NO Production and Protein Expression of eNOS |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 7.0 | Western blotting shows the protein expression of eNOS ( Figure 4 B in isolated coronary arteries of lean |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Role of TNF-alpha in the Metabolic Syndrome-Induced Vascular Dysfunction and the Expression of |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | We administered TNF-alpha (10 10 microg/kg microg kg per day 3 days IP |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | of microvessels to ACh to show the chronic administration of TNF-alpha in lean rats could mimic the responses of vessels from |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | We investigated whether TNF-alpha treatment increased vascular NAD(P)H NAD P H oxidase activation in |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | NAD P H oxidase activation in lean rats by administering TNF-alpha (10 10 microg/kg microg kg per day to lean rats |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22-phox | 1.5 | the mRNA expression of NAD(P)H NAD P H oxidase subunits p22-phox p40-phox p47-phox p67-phox and gp-91-phox |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67-phox | 1.5 | of NAD(P)H NAD P H oxidase subunits p22-phox p40-phox p47-phox p67-phox and gp-91-phox |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp-91-phox | 0.1 | NAD P H oxidase subunits p22-phox p40-phox p47-phox p67-phox and gp-91-phox |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | The results ( Figure 6 indicate that TNF-alpha plays a critical role in the oxidase stress occurring during |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha. | 1.7 | O 2 _amp_#183 production is postulated to be linked to TNF-alpha. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Neither apocynin nor neutralizing antibodies to TNF-alpha affected baseline levels of artery fluorescence (not not shown but |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha-induced | 1.7 | (not not shown but these 2 agents markedly reduced the TNF-alpha-induced fluorescent signals for O 2 _amp_#183 separately |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | we hypothesized that impairments in coronary endothelial function in the obese condition the prediabetic metabolic syndrome is caused by tnf alpha overexpression. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | superoxide o 2 _amp_#183; generation was elevated in vessels from zof rats compared with lean rats and administration of the o 2 _amp_#183; scavenger tempol nad p h oxidase inhibitor apocynin or anti tnf alpha restored endothelium dependent dilation in the zof rats. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | real time pcr and western blotting revealed that mrna and protein of tnf alpha were higher in zof rats than that in lean rats whereas enos protein levels were reduced in the zof versus lean rats. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | immunostaining showed that tnf alpha in zof rat heart is localized in endothelial cells and vascular smooth muscle cells. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | administration of tnf alpha more than 3 days also induced expression of these nad p h subunits and abrogated endothelium dependent dilation. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | in conclusion the results demonstrate the endothelial dysfunction occurring in the metabolic syndrome is the result of effects of the inflammatory cytokine tnf alpha and subsequent production of o 2 _amp_#183; . |
| 6081 | INS | insulin | insulin | 1.0 | e development of the prediabetic metabolic syndrome often referred to as the metabolic syndrome that is a clustering of atherosclerotic cardiovascular risk factors characterized by visceral adiposity insulin resistance low hdl cholesterol and a systemic proinflammatory state. |
| 6081 | INS | insulin | insulin | 1.0 | recent evidence suggests that inflammation plays a role in the development of insulin resistance and predicts the development of type 2 diabetes mellitus. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | tumor necrosis factor tnf alpha a proinflammatory cytokine originally defined by its antitumor activity is an important mediator of many cardiovascular diseases such as myocardial ischemia reperfusion injury chronic heart failure a |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tumor necrosis factor | 1.0 | tumor necrosis factor tnf alpha a proinflammatory cytokine originally defined by its antitumor activity is an important mediator of many cardiovascular diseases such as myocardial ischemia reperfusion injury chronic heart |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | therefore we proposed that tnf alpha may be the inflammatory basis leading from the metabolic syndrome to the atherosclerotic disease. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | to test this we evaluated the endothelium dependent and independent vasodilation the circulating levels of tnf alpha and its expression at the wall of coronary small arteries in zucker lean rats nondiabetic with a normal body mass and zucker obese fatty zof rats. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | we also tested the mechanisms by which tnf alpha induces endothelial dysfunction and the role of o 2 _amp_#183; in small coronary arteries in the metabolic syndrome. |
| 6554 | LEPR | leptin receptor | leptin receptor | 1.0 | the zof rats were homozygous for a missense mutation of the leptin receptor which normally controls appetite rendering it nonfunctional; thus these rats eat profusely and become obese. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | determination of plasma tnf alpha |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | plasma tnf alpha was measured using bio plex mouse 3 plex assay bio rad laboratories calif . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | conjugate beads were added to the microplate to assess the level of tnf alpha in plasma. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | tnf alpha concentrations picograms per milliliter were automatically calculated by bio plex manager software using a standard curve derived from a recombinant cytokine standard. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | treatment with tnf alpha apocynin and tnf alpha neutralization |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | we administered tnf alpha 10 microg/kg ip r_amp_d systems to lean rats for 3 days to determine whether tnf alpha can inhibit coronary arterial dilations mediated by no. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | we also tested whether tnf alpha affected mrna expression of nad p h in lean rats. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | or apocynin 100 mg/kg ip for 3 days to lean rats for 3 days to determine whether apocynin can protect the vasodilation induced in zof rats and test whether apocynin affected the protein expression of tnf alpha and enos. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | the neutralizing antibody to tnf alpha anti tnf alpha used in these studies was 2e2 monoclonal antibody 2e2 mab 94021402 nci biological resources branch . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | at 12 to 16 weeks of age all rats received the neutralizing anti tnf alpha 2e2 mab i.p. 0.625 mg/ml per kilogram per day 3 days ip . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | the rationale for this dose of antibody was based on our estimates of tnf alpha expression in the low nanogram or picogram range ; the dose of antibody was able to neutralize 10 to 100 fold this amount of tnf alpha. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | expression in the low nanogram or picogram range ; the dose of antibody was able to neutralize 10 to 100 fold this amount of tnf alpha. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | to determine whether tnf alpha was played a role in endothelial injury in the metabolic syndrome endothelial dependent and independent dilation was assessed in coronary arteries from anti tnf alpha treated rats. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | to determine the role of tnf alpha and o 2 _amp_#183; anion in altered vasoactive responses in the metabolic syndrome the above vasodilatory functions were examined in the presence of the o 2 _amp_#183; scavenger a membrane permeable |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | the contributions of nad p h oxidase xanthine oxidase and mitochondrial respiratory chain in generating o 2 _amp_#183; were assessed by treating the vessels with the nad p h oxidase inhibitor apocynin 10 micromol/l the xanthine oxidase inhibitor allopur |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | and mitochondrial respiratory chain in generating o 2 _amp_#183; were assessed by treating the vessels with the nad p h oxidase inhibitor apocynin 10 micromol/l the xanthine oxidase inhibitor allopurinol 10 micromol/l or the mitochondrial respiratory chain inhibitor rotenone 1 micromol/l for 60 minute incubation separately. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | mrna expression of tnf alpha and nad p h oxidase subunits by real time pcr |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | the primers of tnf alpha and nad p h oxidase subunits p22 phox p40 phox p 47 phox p67 phox and gp 91 phox were designed primer 3 software and synthesized qiagen . cdna was amplified using qrt pcr kit with sybr green life tec |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 phox | 1.0 | the primers of tnf alpha and nad p h oxidase subunits p22 phox p40 phox p 47 phox p67 phox and gp 91 phox were designed primer 3 software and synthesized qiagen . cdna was amplified using qrt pcr kit with sybr green life technologies inc . |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67 phox | 1.0 | the primers of tnf alpha and nad p h oxidase subunits p22 phox p40 phox p 47 phox p67 phox and gp 91 phox were designed primer 3 software and synthesized qiagen . cdna was amplified using qrt pcr kit with sybr green life technologies inc . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | data were calculated by 2 method and presented as fold change of transcripts for tnf alpha gene and nad p h oxidase gene in zof rats normalized to gapdh compared with lean control rats defined as 1.0 fold . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | protein expression of tnf alpha and enos by western blot analyses |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | tnf alpha and enos protein expression were detected by western blot analysis with the use of tnf alpha primary antibodies santa cruz biotechnology and enos primary antibody abcam in 4 groups of lean rats zof rats zof rats treated with anti tnf alpha 0.625 mg/ml per kilogram per day 3 days ip or zof ra |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | primary antibodies santa cruz biotechnology and enos primary antibody abcam in 4 groups of lean rats zof rats zof rats treated with anti tnf alpha 0.625 mg/ml per kilogram per day 3 days ip or zof rats treated with apocynin 100 mg/kg per day 3 days ip . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | formalin fixed hearts were incubated with blocking solution bsa 3% in tris buffer then incubated with polyclonal goat antibody against tnf alpha r_amp_d systems and the endothelial cell marker von willebrand factor ab6994 abcam or smooth muscle alpha actin 1a4 calbiochem or macrophages mouse anti rat cd68 serotec and then incubated with a sec |
| 12726 | VWF | von Willebrand factor | von willebrand factor | 1.0 | formalin fixed hearts were incubated with blocking solution bsa 3% in tris buffer then incubated with polyclonal goat antibody against tnf alpha r_amp_d systems and the endothelial cell marker von willebrand factor ab6994 abcam or smooth muscle alpha actin 1a4 calbiochem or macrophages mouse anti rat cd68 serotec and then incubated with a secondary fluorescent antibody alexa fluor 488 and alexa fluor 568 molecu |
| 129 | ACTA1 | actin, alpha 1, skeletal muscle | alpha actin | 1.0 | cking solution bsa 3% in tris buffer then incubated with polyclonal goat antibody against tnf alpha r_amp_d systems and the endothelial cell marker von willebrand factor ab6994 abcam or smooth muscle alpha actin 1a4 calbiochem or macrophages mouse anti rat cd68 serotec and then incubated with a secondary fluorescent antibody alexa fluor 488 and alexa fluor 568 molecular probe . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | dhe fluorescence for o 2 _amp_#183; in both endothelial and smooth muscle layers of vessels was measured in lean and zof rats or zof rats with anti tnf alpha or zof rats with apocynin. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | plasma concentration mrna and protein expression of tnf alpha |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | figure 1 a shows elevations of plasma concentration of tnf alpha. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | figure 1 b real time pcr shows elevations of tnf alpha expression. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | figure 1 c western blotting shows the protein expression of tnf alpha in isolated coronary small arteries of lean control rats zof rats zof rats treated with anti tnf alpha 0.625 mg/kg per day 3 days ip or zof rats treated with apocynin 100 mg/kg per day 3 days ip . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | our results suggest that overexpression of tnf alpha induces activation of nad p h oxidase and production of o 2 _amp_#183; leading to endothelial dysfunction in the metabolic syndrome. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | importantly our findings support the concept that tnf alpha plays a pivotal role in endothelial dysfunction in the metabolic syndrome based on the following observations. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | antibody neutralization of tnf alpha prevented coronary endothelial dysfunction and reduced o 2 _amp_#183; generation and protein expression of enos in zof rats. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | blockade of nad p h oxidase mimicked the actions of anti tnf alpha on o 2 _amp_#183; production protein expression of tnf alpha and enos and endothelial function in zof rats. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | molecular evidence indicated that the expression of tnf alpha mrna and protein and mrna expression of nad p h oxidase subunits p22 phox and p40 phox were significantly increased but protein expression of enos was diminished in zof rats. |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 phox | 1.0 | molecular evidence indicated that the expression of tnf alpha mrna and protein and mrna expression of nad p h oxidase subunits p22 phox and p40 phox were significantly increased but protein expression of enos was diminished in zof rats. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | tnf alpha and the metabolic syndrome |
| 6081 | INS | insulin | insulin | 1.0 | tnf alpha is overexpressed in obesity and likely mediates insulin resistance in the major animal models of obesity; neutralization of tnf alpha with soluble tnf alpha receptors results in the restoration of insulin sensitivity and thereby demonstrates that the proi |
| 6081 | INS | insulin | insulin | 1.0 | resistance in the major animal models of obesity; neutralization of tnf alpha with soluble tnf alpha receptors results in the restoration of insulin sensitivity and thereby demonstrates that the proinflammatory cytokine tnf alpha is the mediator of insulin resistance. |
| 6081 | INS | insulin | insulin | 1.0 | sensitivity and thereby demonstrates that the proinflammatory cytokine tnf alpha is the mediator of insulin resistance. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | tnf alpha is overexpressed in obesity and likely mediates insulin resistance in the major animal models of obesity; neutralization of tnf alpha with soluble tnf alpha receptors results in the restoration of insulin sensitivity and thereby demonstrates that the proinflammatory cytokine tnf alpha is the mediator of insulin resistance. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | receptors results in the restoration of insulin sensitivity and thereby demonstrates that the proinflammatory cytokine tnf alpha is the mediator of insulin resistance. |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | interleukin 6 | 1.0 | studies in human show increased tnf alpha interleukin 6 il 6 c reactive protein crp and migration inhibitory factor mif plasma levels indicating metabolic syndrome is an inflammatory state. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | studies in human show increased tnf alpha interleukin 6 il 6 c reactive protein crp and migration inhibitory factor mif plasma levels indicating metabolic syndrome is an inflammatory state. |
| 2367 | CRP | C-reactive protein, pentraxin-related | c reactive protein | 1.0 | studies in human show increased tnf alpha interleukin 6 il 6 c reactive protein crp and migration inhibitory factor mif plasma levels indicating metabolic syndrome is an inflammatory state. |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | il 6 | 1.0 | studies in human show increased tnf alpha interleukin 6 il 6 c reactive protein crp and migration inhibitory factor mif plasma levels indicating metabolic syndrome is an inflammatory state. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | we found increased tnf alpha mrna expression 5 fold plasma concentration of tnf alpha 8 fold and protein expression of tnf alpha more than 3 fold in small coronary arteries in zof rats. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | if tnf alpha is as we and others suspect 1 of the initiators of a cytokine cascade then it may also be 1 of the genes that is induced very quickly following perturbation. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | our immunostaining results show tnf alpha in zof rat heart is localized in ecs and vascular smooth muscle cells. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | we believe o 2 _amp_#183; production in vascular endothelial cells and smooth muscle cells by tnf alpha would limit no bioavailability and reduce no dependent dilation. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | finally tnf alpha can be "stored" within cells in a "pre" form and the enzyme tnf alpha converting enzyme can rapidly increase levels of the active cytokine. |
| 195 | ADAM17 | ADAM metallopeptidase domain 17 (tumor necrosis factor, alpha, converting enzyme) | tnf alpha converting enzyme | 1.0 | finally tnf alpha can be "stored" within cells in a "pre" form and the enzyme tnf alpha converting enzyme can rapidly increase levels of the active cytokine. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | there is no previous report on the endogenous role of tnf alpha in this respect and it has been unclear whether tnf alpha plays a direct role in endothelial dysfunction in the metabolic syndrome. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | recent evidence supports the idea that the effect of tnf alpha is no dependent by producing a rapid inhibitory action on no synthase nos in the endothelium via activation of a sphingomyelinase/ceramide signaling pathway; this mechanism is supposed to mediate the |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | ndent by producing a rapid inhibitory action on no synthase nos in the endothelium via activation of a sphingomyelinase/ceramide signaling pathway; this mechanism is supposed to mediate the action of tnf alpha thereby contributing to vascular endothelial dysfunction in coronary circulation under different pathological conditions with increased cytokines. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | in the present study we documented that tnf alpha is critical for the development of endothelial dysfunction in the model of the metabolic syndrome. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | tnf alpha expression was significantly increased in zof rats; anti tnf alpha restored no mediated coronary arterial dilation in zof rats but did not affect the endothelium dependent vasodilation in lean controls. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | furthermore administration of anti tnf alpha protected endothelial dysfunction induced by tnf alpha in isolated vessels from lean control rats confirming that the monoclonal anti tnf alpha was specific. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | impaired endothelium dependent vasodilation was restored in zof rats after the treatment with tnf alpha antibodies for 3 days ip and 3 days treatment with tnf alpha ip mimicked endothelial dysfunction in lean rats both demonstrating the pivotal role of this inflammatory cytokine in the vascular pathology of the metabolic syndrome. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | this result is in agreement with those of previous studies showing that tnf alpha can decrease the release of endothelial no and induce impairment of endothelium dependent relaxation in a variety of vascular beds. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | anti tnf alpha or apocynin attenuated the production of o 2 _amp_#183; in zof rats thereby confirming the critical role of o 2 _amp_#183; in the endothelial dysfunction occurring in the metabolic syndrome. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | the link between tnf alpha overexpression and o 2 _amp_#183; production has been investigated by zhang et al who found that tiron a cell permeable o 2 _amp_#183; scavenger and polyethylene glycol conjugated superoxide dismutas |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | o 2 _amp_#183; production has been investigated by zhang et al who found that tiron a cell permeable o 2 _amp_#183; scavenger and polyethylene glycol conjugated superoxide dismutase peg sod prevented tnf alpha induced impairment of endothelium dependent vasorelaxation in coronary arterioles. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | k between tnf alpha overexpression and o 2 _amp_#183; production has been investigated by zhang et al who found that tiron a cell permeable o 2 _amp_#183; scavenger and polyethylene glycol conjugated superoxide dismutase peg sod prevented tnf alpha induced impairment of endothelium dependent vasorelaxation in coronary arterioles. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | our results are consistent with these studies and support our hypotheses that tnf alpha and o 2 _amp_#183; are connected in the production of oxidative stress and endothelial dysfunction in the metabolic syndrome. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | effect of enos on tnf alpha induced endothelial dysfunction in the metabolic syndrome |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | the vascular endothelium is a major target for the actions of tnf alpha. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | tnf alpha can decrease the release of endothelial no and induce impairment of endothelium dependent vasodilation in a variety of vascular beds ; however the signaling pathways that couple tnf alpha stimulation to endothelial dysfunction in small coronary arteries remain to be understood. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | zhang et al demonstrated that tnf alpha inhibited no mediated endothelium dependent vasorelaxation in coronary arterioles by activating sphingomyelinase and enhancing o 2 _amp_#183; generation in coronary endothelial cells. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | in the presence of l nmma tnf alpha had no further inhibitory effect on the responses to endothelium dependent vasodilators suggesting that the effect of tnf alpha is no dependent. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | tnf alpha is known to affect enos expression by affecting the half life of its mrna. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | we know that tnf alpha impairs endothelial function by reducing no bioavailability but little information is available in the literature on how tnf alpha affects endothelial nos enos activity in coronary arteries. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | ugh there are multiple intracellular sources for formation of oxygen free radicals eg mitochondria xanthine oxidase nad[p]h oxidase etc our results support the idea that the major enzyme activated by tnf alpha in the metabolic syndrome is nad p h oxidase. |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | although there are multiple intracellular sources for formation of oxygen free radicals eg mitochondria xanthine oxidase nad[p]h oxidase etc our results support the idea that the major enzyme activated by tnf alpha in the metabolic syndrome is nad p h oxidase. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | our results indicate that the pathway for tnf alpha induced endothelial dysfunction is mediated by activation of nad p h oxidase and the subsequent production of o 2 _amp_#183; . |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | to the contrary we did not find any improvement in endothelial function after incubation with rotenone and allopurinol suggesting that mitochondria and the xanthine oxidase system are not likely to be the source of o 2 _amp_#183; production. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | our results demonstrate the production of tnf alpha is essential in eliciting this oxidative stress. |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67 phox | 1.0 | guzik et al reported that the protein expression of nad p h oxidase subunits p22 p47 and p67 phox are significantly increased in diabetic human tissue versus normal control. |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 phox | 1.0 | our real time pcr results indicate that mrna expression of nad p h oxidase subunit p22 phox and p40 phox are increased _amp_2 fold in zof rats versus lean rats. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | most interestingly the tnf alpha treatment also increases the mrna expression of vascular nad p h oxidase subunits p22 phox and p40 phox in the control animals. |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 phox | 1.0 | most interestingly the tnf alpha treatment also increases the mrna expression of vascular nad p h oxidase subunits p22 phox and p40 phox in the control animals. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | further studies are needed to determine the mechanism linking tnf alpha receptor activation to nad p h oxidase. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | the present study indicates that the model of the metabolic syndrome increases tnf alpha which stimulates endothelial generation of through activation of nad p h oxidase in the endothelium and contributes to the endothelial dysfunction. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | to our knowledge this is the first functional study to link the mechanism s of the model of the metabolic syndrome_amp_#151;in terms of endothelial dysfunction_amp_#151;to tnf alpha the subsequent activation of nad p h oxidase and thus the production of in coronary artery endothelium. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | taken together these results further support our hypothesis that tnf alpha and o 2 _amp_#183; are connected in the production of oxidative stress and endothelial dysfunction in the metabolic syndrome. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | in conclusion we found that tnf alpha overexpression impairs endothelium dependent vasodilation in coronary arterioles of rats affected by the model of the metabolic syndrome. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | the impaired endothelial function can be restored toward normal by administration of tnf alpha antibodies. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | the mechanism by which tnf alpha affects endothelial function seems to be an increased superoxide production by nad p h oxidases which in turn leads to a reduced no bioactivity by direct scavenging. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | these findings may provide further insight into a novel therapeutic target for cardiovascular diseases associated with elevated levels of tnf alpha. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | a plasma concentration of inflammatory cytokine tnf alpha is significantly increased in zof rats. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | b real time pcr of tnf alpha mrna from left ventricular coronary arteries in lean control and zof rats. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | b shows fold change of tnf alpha mrna expression which was significantly higher in zof rats than in lean controls. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | c western blotting showed the protein expression of tnf alpha normalized to _amp_#223; actin in isolated small coronary arteries in lean control and zof rats. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | bars represent the increased expression of tnf alpha in zof rats as a percentage of control. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | the protein expression of tnf alpha was higher in coronary arteries of zof rats than in lean controls but tnf alpha expression in anti tnf alpha or apocynin treated zof rats was similar to lean control rats. |
| 143 | ACTC1 | actin, alpha, cardiac muscle 1 | smooth muscle actin | 1.0 | dual fluorescence combining tnf alpha with markers for macrophages cd68 vascular smooth muscle alpha smooth muscle actin [ alpha sma] or endothelial cells von willebrand factor [vwf] using specific antibodies followed by a fluorescent labeled secondary antibody. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | dual fluorescence combining tnf alpha with markers for macrophages cd68 vascular smooth muscle alpha smooth muscle actin [ alpha sma] or endothelial cells von willebrand factor [vwf] using specific antibodies followed by a fluorescent la |
| 12726 | VWF | von Willebrand factor | von willebrand factor | 1.0 | dual fluorescence combining tnf alpha with markers for macrophages cd68 vascular smooth muscle alpha smooth muscle actin [ alpha sma] or endothelial cells von willebrand factor [vwf] using specific antibodies followed by a fluorescent labeled secondary antibody. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | a through c dual labeling of alpha sma green and tnf alpha red in lean rat heart tissue. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | e through g dual labeling of alpha sma green and tnf alpha red in zof rat heart tissue. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | the insets d and h show a colocalization of tnf alpha red and alpha sma green . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | i through k dual labeling of endothelial cells red and tnf alpha green in zof rat heart tissues. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | the inset l shows a colocalization of tnf alpha green and vwf factor red in zof rat heart tissues. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | m through o dual labeling of cd68 red and tnf alpha green in zof rat heart tissue; the arrow in o and inset p show a specific macrophage staining and absence of tnf alpha staining. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | the immunostaining results show that tnf alpha in zof rat heart is expressed in vascular smooth muscle and endothelial cells. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | b protein expression of enos in isolated coronary arteries of lean control zof zof rats treated with anti tnf alpha 0.625 mg/kg per day 3 days ip or zof treated with apocynin 100 mg/kg per day 3 days ip . enos protein was lower in zof rats than in lean rats. enos expression in anti tnf alpha or apocynin treated zo |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | 0.625 mg/kg per day 3 days ip or zof treated with apocynin 100 mg/kg per day 3 days ip . enos protein was lower in zof rats than in lean rats. enos expression in anti tnf alpha or apocynin treated zof rats was higher than in zof rats but lower compared with that in lean controls n=5 . * p _lt_0.05 vs lean rats; # p _lt_0.05 vs zof rats. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | ach induced dilation was significantly blunted by 3 days treatment with tnf alpha 10 microg/kg n=5 but 3 days treatment of anti tnf alpha 0.625 mg/kg n=6 protected endothelial dysfunction induced by tnf alpha in lean control rats. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | three days of treatment with the nad p h oxidase inhibitor apocynin 100 mg/kg restored the impaired endothelial function induced by tnf alpha in vessels isolated from lean rats n=5 a . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | anti tnf alpha restored no mediated coronary arterial dilation in zof rats but did not affect the vasodilation in lean control rats b . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | flow dependent dilation in zof rats was also decreased relative to lean controls c . * p _lt_0.05 lean rats vs zof rats; # p _lt_0.05 lean rats+tnf alpha vs lean rats+tnf alpha+anti tnf alpha; # p _lt_0.05 lean rats+tnf alpha vs lean rats+tnf alpha+apocynin. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | ; # p _lt_0.05 lean rats+tnf alpha vs lean rats+tnf alpha+apocynin. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | esent the increased expression in zof rats as a fold change of lean control. mrna expression for nad p h oxidase p22 phox and p40 phox is higher in zof rats than in lean control rats and treatment by tnf alpha 10 microg/kg 3 days ip significantly increased the mrna expression of nad p h oxidase subunits p22 phox and p40 phox in lean rats. |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 phox | 1.0 | bars represent the increased expression in zof rats as a fold change of lean control. mrna expression for nad p h oxidase p22 phox and p40 phox is higher in zof rats than in lean control rats and treatment by tnf alpha 10 microg/kg 3 days ip significantly increased the mrna expression of nad p h oxidase subunits p22 phox and p40 |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 phox | 1.0 | and p40 phox is higher in zof rats than in lean control rats and treatment by tnf alpha 10 microg/kg 3 days ip significantly increased the mrna expression of nad p h oxidase subunits p22 phox and p40 phox in lean rats. |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | incubation of coronary arteries with the o 2 _amp_#183; scavenger tempol 1 mmol/l n=7 a or the nad p h oxidase inhibitor apocynin 10 micromol/l n=8 b restored vasodilation in zof rats but the xanthine oxidase inhibitor allopurinol 10 micromol/l n=5 or oxypurinol 100 micromol/l n=4 or the mitochondrial respiratory chain inhibitor rotenone 1 micromol/l n=4 did not data not shown . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | both anti tnf alpha and apocynin significantly reduced the fluorescent signals in zof rats. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | however neither apocynin nor anti tnf alpha markedly reduced the fluorescent signals n=4 . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | administration of anti tnf alpha or apocynin reduced the production of o 2 _amp_#183; to the level observed in the lean controls. n=6 b . * p _lt_0.05 vs lean rats; # p _lt_0.05 vs zof rats. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | cellular source of tnf alpha expression in the metabolic syndrome |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | markers for endothelial cells ecs von willebrand factor vascular smooth muscle cells vsmcs alpha actin or macrophages mouse anti rat cd68 along with tnf alpha to establish the cell type expressing the tnf alpha showed that tnf alpha in rat heart was localized in endothelial cells and vascular smooth muscle cells figure 2 . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | to establish the cell type expressing the tnf alpha showed that tnf alpha in rat heart was localized in endothelial cells and vascular smooth muscle cells figure 2 . |
| 12726 | VWF | von Willebrand factor | von willebrand factor | 1.0 | markers for endothelial cells ecs von willebrand factor vascular smooth muscle cells vsmcs alpha actin or macrophages mouse anti rat cd68 along with tnf alpha to establish the cell type expressing the tnf alpha showed that tnf alpha in rat heart was local |
| 129 | ACTA1 | actin, alpha 1, skeletal muscle | alpha actin | 1.0 | markers for endothelial cells ecs von willebrand factor vascular smooth muscle cells vsmcs alpha actin or macrophages mouse anti rat cd68 along with tnf alpha to establish the cell type expressing the tnf alpha showed that tnf alpha in rat heart was localized in endothelial cells and vascular smooth m |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | western blotting shows the protein expression of enos figure 4 b in isolated coronary arteries of lean control zof rats zof rats treated with anti tnf alpha 0.625 mg/kg per day 3 days ip or zof rats treated with the nad p h oxidase inhibitor apocynin 100 mg/kg per day 3 days ip . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | role of tnf alpha in the metabolic syndrome induced vascular dysfunction and the expression of nad p h oxidase |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | we administered tnf alpha 10 microg/kg per day 3 days ip and assessed responses of microvessels to ach to show the chronic administration of tnf alpha in lean rats could mimic the responses of vessels from zof rats figure 5 a . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | we also found that administration of anti tnf alpha 2e2 monoclonal antibody restored endothelial function in zof rats figure 5 b . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | we investigated whether tnf alpha treatment increased vascular nad p h oxidase activation in lean rats by administering tnf alpha 10 microg/kg per day to lean rats for 3 days and evaluating the mrna expression of nad p h oxidase subunits p22 phox p40 phox p47 phox p67 phox and gp 91 phox. |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 phox | 1.0 | tment increased vascular nad p h oxidase activation in lean rats by administering tnf alpha 10 microg/kg per day to lean rats for 3 days and evaluating the mrna expression of nad p h oxidase subunits p22 phox p40 phox p47 phox p67 phox and gp 91 phox. |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67 phox | 1.0 | d p h oxidase activation in lean rats by administering tnf alpha 10 microg/kg per day to lean rats for 3 days and evaluating the mrna expression of nad p h oxidase subunits p22 phox p40 phox p47 phox p67 phox and gp 91 phox. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | the results figure 6 indicate that tnf alpha plays a critical role in the oxidase stress occurring during the metabolic syndrome by inducing expression of nad p h oxidase. |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | roles of superoxide xanthine oxidase mitochondrial respiratory chain and nad p h oxidase in the metabolic syndrome induced vascular dysfunction |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | o 2 _amp_#183; production is postulated to be linked to tnf alpha. |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | to establish the pathway for o 2 _amp_#183; production we administered the nad p h oxidase inhibitor apocynin 10 micromol/l the xanthine oxidase inhibitor allopurinol 10 micromol/l or the mitochondrial respiratory chain inhibitor rotenone 1 micromol/l to determine whether vasodilation to ach would be restored in zof rats figure 7 . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | neither apocynin nor neutralizing antibodies to tnf alpha affected baseline levels of artery fluorescence not shown but these 2 agents markedly reduced the tnf alpha induced fluorescent signals for o 2 _amp_#183; separately. |