)| PMID |
17237245 ( ) |
|---|---|
| Title | Reactive oxygen species-selective regulation of aortic inflammatory gene expression in Type 2 diabetes. |
| Abstract | Vascular diseases are a major complication of diabetes mellitus (DM), although their etiology is poorly understood. NADPH oxidase-derived reactive oxygen species (ROS) production and inflammation are potential mediators of DM-associated vascular diseases. Using db/db mice as a Type 2 diabetes model, we examined the relationship between NADPH oxidase-derived ROS and vascular inflammation. When compared with control m+/+ mice, aortas from 4- and 12-wk-old db/db mice had higher NADPH oxidase activity and increased superoxide levels, leading to NADPH oxidase-dependent impaired vasodilation at 12 wk. Diabetes progression from 4 to 12 wk led to increased Nox1, Nox4, and p22(phox) subunit mRNAs and induced the expression of a group of matrix remodeling-related cytokines: connective tissue growth factor (CTGF), bone morphogenetic protein 4 (BMP-4), and osteopontin (OPN). After 8 wk of treatment with the superoxide scavenger Tempol, 12-wk-old db/db mice had lower superoxide production, reduced plasma glucose and lipids, and lower BMP-4 and OPN protein expression when compared with nontreated mice. No changes were observed with Tempol in CTGF or m+/+ mice. The ability of Tempol to reverse ROS production as well as OPN and BMP-4, but not CTGF, induction suggests that DM-induced vascular inflammation involves both ROS-sensitive and -insensitive pathways. Pierce Dr., Atlanta, GA 30322, 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 |
|---|---|---|---|---|
| 1071 | BMP4 | bone morphogenetic protein 4 | 27 | bone morphogenetic protein 4 | BMP-4 | |
| 2500 | CTGF | connective tissue growth factor | 25 | connective tissue growth factor | CTGF | |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | 23 | OPN | osteopontin | |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | 22 | nadph oxidase | |
| 7891 | NOX4 | NADPH oxidase 4 | 11 | Nox4 | nox4 | NOX4 | |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | 8 | mcp 1 | MCP-1 | |
| 7889 | NOX1 | NADPH oxidase 1 | 8 | nox1 | Nox1 | |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | 7 | tumor necrosis factor alpha | TNF-alpha | tnf alpha | |
| 6081 | INS | insulin | 7 | insulin | |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | 7 | p22 | |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | 5 | VCAM-1 | |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | 5 | nox2 | Nox2 | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 3 | SOD | SOD-inhibitable | |
| 437 | ALPI | alkaline phosphatase, intestinal | 2 | alkaline phosphatase | |
| 29477 | LEPROT | leptin receptor overlapping transcript | 2 | Lepr | |
| 6553 | LEP | leptin | 1 | leptin | |
| 6554 | LEPR | leptin receptor | 1 | leptin receptor | |
| 30000 | BBS9 | Bardet-Biedl syndrome 9 | 1 | C-18 | |
| 7176 | MMP9 | matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) | 1 | matrix metalloproteinase 9 | |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | 1 | NF-kappaB | |
| 3122 | LEFTY2 | left-right determination factor 2 | 1 | transforming growth factor beta superfamily | |
| 613 | APOE | apolipoprotein E | 1 | apolipoprotein e | |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | 1 | p47 | |
| 6877 | MAPK3 | mitogen-activated protein kinase 3 | 1 | ERK1 | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 7889 | NOX1 | NADPH oxidase 1 | Nox1 | 0.9 | Diabetes progression from 4 to 12 wk led to increased Nox1 Nox4 and p22 subunit mRNAs and induced the expression of |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 1.4 | progression from 4 to 12 wk led to increased Nox1 Nox4 and p22 subunit mRNAs and induced the expression of a |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 1.0 | 4 to 12 wk led to increased Nox1 Nox4 and p22 subunit mRNAs and induced the expression of a group of |
| 2500 | CTGF | connective tissue growth factor | CTGF | 5.3 | group of matrix remodeling-related cytokines connective tissue growth factor (CTGF), CTGF bone morphogenetic protein 4 (BMP-4), BMP-4 and osteopontin (OPN) OPN |
| 1071 | BMP4 | bone morphogenetic protein 4 | BMP-4 | 2.7 | tissue growth factor (CTGF), CTGF bone morphogenetic protein 4 (BMP-4), BMP-4 and osteopontin (OPN) OPN |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | OPN | 0.8 | CTGF bone morphogenetic protein 4 (BMP-4), BMP-4 and osteopontin (OPN) OPN |
| 1071 | BMP4 | bone morphogenetic protein 4 | BMP-4 | 2.7 | lower superoxide production reduced plasma glucose and lipids and lower BMP-4 and OPN protein expression when compared with nontreated mice |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | OPN | 0.8 | production reduced plasma glucose and lipids and lower BMP-4 and OPN protein expression when compared with nontreated mice |
| 2500 | CTGF | connective tissue growth factor | CTGF | 5.3 | No changes were observed with Tempol in CTGF or m +/+ mice |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | OPN | 0.8 | ability of Tempol to reverse ROS production as well as OPN and BMP-4 but not CTGF induction suggests that DM-induced vascular |
| 1071 | BMP4 | bone morphogenetic protein 4 | BMP-4 | 2.7 | Tempol to reverse ROS production as well as OPN and BMP-4 but not CTGF induction suggests that DM-induced vascular inflammation involves |
| 2500 | CTGF | connective tissue growth factor | CTGF | 5.3 | ROS production as well as OPN and BMP-4 but not CTGF induction suggests that DM-induced vascular inflammation involves both ROS-sensitive and |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | through regulation of inflammatory cytokines such as tumor necrosis factor-alpha TNF-alpha and interleukins ( 32 |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | Since the discovery that TNF-alpha expression also occurs in adipose tissue ( 21 the contribution |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | OPN | 0.8 | Osteopontin (OPN), OPN a widely distributed acidic phosphoprotein found in atherosclerotic plaques contributes |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | OPN | 0.8 | OPN is upregulated in diabetic animal models ( 31 and humans |
| 1071 | BMP4 | bone morphogenetic protein 4 | BMP-4 | 2.7 | Another important matrix cytokine is bone morphogenetic protein 4 (BMP-4), BMP-4 a member of the transforming growth factor-beta superfamily which is |
| 2500 | CTGF | connective tissue growth factor | CTGF | 5.3 | Finally connective tissue growth factor (CTGF) CTGF is a potent chemotactic and extracellular matrix-inducing growth factor found |
| 2500 | CTGF | connective tissue growth factor | CTGF | 5.3 | CTGF has been implicated in diabetic nephropathy and retinopathy ( 28 |
| 29477 | LEPROT | leptin receptor overlapping transcript | Lepr | 1.6 | Db/db Db db mice (related related genotype a / a Lepr /+ Lepr a model of Type 2 diabetes and the |
| 29477 | LEPROT | leptin receptor overlapping transcript | Lepr | 1.6 | db mice (related related genotype a / a Lepr /+ Lepr a model of Type 2 diabetes and the metabolic syndrome |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD-inhibitable | 0.3 | Superoxide formation was assayed as NADPH-dependent SOD-inhibitable formation of 3-carboxy-proxyl (CP CP |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.3 | SOD (50 50 U/ml) U ml added directly to the sample |
| 30000 | BBS9 | Bardet-Biedl syndrome 9 | C-18 | 0.3 | performed with the use of an acetonitrile gradient and a C-18 reverse-phase column (Nucleosil Nucleosil 250-4.5 mm on a Beckman HPLC |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.3 | In some samples polyethylene glycol (PEG)-SOD PEG -SOD (100 100 U/ml) U ml was added 1 h before |
| 7889 | NOX1 | NADPH oxidase 1 | nox1 | 0.9 | instrument (Roche) Roche with SYBR green dye and specific mouse nox1 nox2 nox4 p22 VCAM-1 MCP-1 CTGF BMP-4 and OPN primers |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | nox2 | 1.0 | (Roche) Roche with SYBR green dye and specific mouse nox1 nox2 nox4 p22 VCAM-1 MCP-1 CTGF BMP-4 and OPN primers ( |
| 7891 | NOX4 | NADPH oxidase 4 | nox4 | 1.4 | Roche with SYBR green dye and specific mouse nox1 nox2 nox4 p22 VCAM-1 MCP-1 CTGF BMP-4 and OPN primers ( Table |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 1.0 | with SYBR green dye and specific mouse nox1 nox2 nox4 p22 VCAM-1 MCP-1 CTGF BMP-4 and OPN primers ( Table 1 |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.2 | SYBR green dye and specific mouse nox1 nox2 nox4 p22 VCAM-1 MCP-1 CTGF BMP-4 and OPN primers ( Table 1 and |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | MCP-1 | 1.3 | green dye and specific mouse nox1 nox2 nox4 p22 VCAM-1 MCP-1 CTGF BMP-4 and OPN primers ( Table 1 and normalized |
| 2500 | CTGF | connective tissue growth factor | CTGF | 5.3 | dye and specific mouse nox1 nox2 nox4 p22 VCAM-1 MCP-1 CTGF BMP-4 and OPN primers ( Table 1 and normalized to |
| 1071 | BMP4 | bone morphogenetic protein 4 | BMP-4 | 2.7 | and specific mouse nox1 nox2 nox4 p22 VCAM-1 MCP-1 CTGF BMP-4 and OPN primers ( Table 1 and normalized to 18S |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | OPN | 0.8 | mouse nox1 nox2 nox4 p22 VCAM-1 MCP-1 CTGF BMP-4 and OPN primers ( Table 1 and normalized to 18S ribosomal RNA |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | However inflammatory molecules such as TNF-alpha can induce insulin resistance ( 46 and diabetes upregulates inflammatory |
| 2500 | CTGF | connective tissue growth factor | CTGF | 5.3 | More importantly expression of a group of inflammatory cytokines CTGF OPN and BMP-4 was increased in aortas from diabetic animals |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | OPN | 0.8 | More importantly expression of a group of inflammatory cytokines CTGF OPN and BMP-4 was increased in aortas from diabetic animals |
| 1071 | BMP4 | bone morphogenetic protein 4 | BMP-4 | 2.7 | expression of a group of inflammatory cytokines CTGF OPN and BMP-4 was increased in aortas from diabetic animals |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 1.0 | Tokushima Fatty rats aortic NADH oxidase activity and gp91 /p22 p22 expression is increased ( 25 whereas in Goto-Kakizaki rats no |
| 7889 | NOX1 | NADPH oxidase 1 | Nox1 | 0.9 | Expression of the catalytic Nox1 and Nox4 subunits as well as the stabilizing subunit p22 |
| 7891 | NOX4 | NADPH oxidase 4 | NOX4 | 1.4 | Expression of the catalytic Nox1 and Nox4 subunits as well as the stabilizing subunit p22 |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 1.4 | Expression of the catalytic Nox1 and Nox4 subunits as well as the stabilizing subunit p22 increased with |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 1.0 | Nox1 and Nox4 subunits as well as the stabilizing subunit p22 increased with age and diabetes similar to previous findings in |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.6 | providing clear evidence for involvement of NADPH oxidases that contain p47 as part of their active complex (Nox1 Nox1 or Nox2 |
| 7889 | NOX1 | NADPH oxidase 1 | Nox1 | 0.9 | that contain p47 as part of their active complex (Nox1 Nox1 or Nox2 in the vasculature |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | Nox2 | 1.0 | p47 as part of their active complex (Nox1 Nox1 or Nox2 in the vasculature |
| 2500 | CTGF | connective tissue growth factor | CTGF | 5.3 | e.g. NF-kappaB and some of which like those that regulate CTGF (e.g., e.g. ERK1/2 ERK1 2 in vascular smooth muscle ( |
| 6877 | MAPK3 | mitogen-activated protein kinase 3 | ERK1 | 1.0 | of which like those that regulate CTGF (e.g., e.g. ERK1/2 ERK1 2 in vascular smooth muscle ( 44 are not |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.0 | expression some of which are regulated by ROS (e.g., e.g. NF-kappaB and some of which like those that regulate CTGF (e.g., |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | MCP-1 | 1.3 | work on inflammatory gene expression in diabetic animals centered on MCP-1 and VCAM-1 ( 53 |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.2 | inflammatory gene expression in diabetic animals centered on MCP-1 and VCAM-1 ( 53 |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.2 | db mice crossed into the apolipoprotein E-deficient background in which VCAM-1 tissue factor and matrix metalloproteinase-9 were induced when plaques were |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | OPN | 0.8 | OPN expression is increased in atherosclerotic plaques ( 15 and regulates |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | OPN | 0.8 | OPN has previously been shown to be induced by oxidative injury |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | OPN | 0.8 | Of importance we found that OPN is upregulated at 12 wk in aortas from diabetic animals |
| 1071 | BMP4 | bone morphogenetic protein 4 | BMP-4 | 2.7 | Another important proinflammatory molecule is BMP-4 which mediates monocyte adhesion ( 42 43 and is upregulated |
| 1071 | BMP4 | bone morphogenetic protein 4 | BMP-4 | 2.7 | BMP-4 was one of the most highly regulated genes both at |
| 1071 | BMP4 | bone morphogenetic protein 4 | BMP-4 | 2.7 | Not only are both BMP-4 and OPN upregulated by ROS but also they activate NADPH |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | OPN | 0.8 | Not only are both BMP-4 and OPN upregulated by ROS but also they activate NADPH oxidases ( |
| 2500 | CTGF | connective tissue growth factor | CTGF | 5.3 | Recent work has shown that CTGF can negatively regulate BMP-4 signaling ( 1 raising the possibility |
| 1071 | BMP4 | bone morphogenetic protein 4 | BMP-4 | 2.7 | Recent work has shown that CTGF can negatively regulate BMP-4 signaling ( 1 raising the possibility that the increase in |
| 2500 | CTGF | connective tissue growth factor | CTGF | 5.3 | signaling ( 1 raising the possibility that the increase in CTGF that we observed in diabetic mice compensates for increased BMP-4 |
| 1071 | BMP4 | bone morphogenetic protein 4 | BMP-4 | 2.7 | CTGF that we observed in diabetic mice compensates for increased BMP-4 expression |
| 2500 | CTGF | connective tissue growth factor | CTGF | 5.3 | CTGF itself is a potent chemotactic and extracellular matrix-inducing growth factor |
| 7889 | NOX1 | NADPH oxidase 1 | nox1 | 0.9 | B nox1 nox2 nox4 or p22 mRNAs from db/db db db and |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | nox2 | 1.0 | B nox1 nox2 nox4 or p22 mRNAs from db/db db db and misty |
| 7891 | NOX4 | NADPH oxidase 4 | nox4 | 1.4 | B nox1 nox2 nox4 or p22 mRNAs from db/db db db and misty aortas |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 1.0 | B nox1 nox2 nox4 or p22 mRNAs from db/db db db and misty aortas were measured |
| 7891 | NOX4 | NADPH oxidase 4 | nox4 | 1.4 | To detect interaction between dependent variables in nox4 mRNA data were analyzed using one-way ANOVA followed by post |
| 2500 | CTGF | connective tissue growth factor | CTGF | 5.3 | and misty aortas and osteopontin connective tissue growth factor (CTGF), CTGF bone morphogenetic protein 4 (BMP-4) BMP-4 mRNAs were measured using |
| 1071 | BMP4 | bone morphogenetic protein 4 | BMP-4 | 2.7 | tissue growth factor (CTGF), CTGF bone morphogenetic protein 4 (BMP-4) BMP-4 mRNAs were measured using real-time PCR and normalized to 18S |
| 1071 | BMP4 | bone morphogenetic protein 4 | BMP-4 | 2.7 | Effect of Tempol on osteopontin and BMP-4 expression in aortas from 12-wk-old mice |
| 1071 | BMP4 | bone morphogenetic protein 4 | BMP-4 | 2.7 | A aortas were harvested and proteins were analyzed for BMP-4 by Western blot |
| 1071 | BMP4 | bone morphogenetic protein 4 | BMP-4 | 2.7 | pressure fixed and sections were subjected to immunohistochemistry using a BMP-4 monoclonal antibody |
| 1071 | BMP4 | bone morphogenetic protein 4 | BMP-4 | 2.7 | Brown staining indicates BMP-4 immunoreactivity |
| 2500 | CTGF | connective tissue growth factor | CTGF | 5.3 | Effect of Tempol on CTGF expression in aortas from 12-wk-old mice |
| 2500 | CTGF | connective tissue growth factor | CTGF | 5.3 | A CTGF mRNA from db/db db db and misty aortas was measured |
| 2500 | CTGF | connective tissue growth factor | CTGF | 5.3 | B aortas were harvested and proteins were analyzed for CTGF by Western blot |
| 1071 | BMP4 | bone morphogenetic protein 4 | BMP-4 | 2.7 | Primary antibodies were against BMP-4 (Santa Santa Cruz monoclonal catalog no sc-12721 and CTGF (polyclonal, |
| 2500 | CTGF | connective tissue growth factor | CTGF | 5.3 | against BMP-4 (Santa Santa Cruz monoclonal catalog no sc-12721 and CTGF (polyclonal, polyclonal catalog no sc-14939 Santa Cruz |
| 1071 | BMP4 | bone morphogenetic protein 4 | BMP-4 | 2.7 | After 10 mmol/l mmol l citrate buffer antigen retrieval BMP-4 was immunolocalized using a monoclonal antibody (monoclonal, monoclonal catalog no |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | OPN | 0.8 | For OPN a polyclonal antibody was used (catalog catalog no 18621 IBL-Japan |
| 7889 | NOX1 | NADPH oxidase 1 | nox1 | 0.9 | activity is due to increased catalytic subunit expression we measured nox1 nox2 and nox4 as well as p22 mRNA levels |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | nox2 | 1.0 | is due to increased catalytic subunit expression we measured nox1 nox2 and nox4 as well as p22 mRNA levels |
| 7891 | NOX4 | NADPH oxidase 4 | NOX4 | 1.4 | is due to increased catalytic subunit expression we measured nox1 nox2 and nox4 as well as p22 mRNA levels |
| 7891 | NOX4 | NADPH oxidase 4 | nox4 | 1.4 | to increased catalytic subunit expression we measured nox1 nox2 and nox4 as well as p22 mRNA levels |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 1.0 | expression we measured nox1 nox2 and nox4 as well as p22 mRNA levels |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 1.0 | 12 wk in db/db db db and control misty mice p22 was significantly upregulated in db/db db db mice compared with |
| 7889 | NOX1 | NADPH oxidase 1 | nox1 | 0.9 | Similarly nox1 and nox4 were increased at 12 wk and their expression |
| 7891 | NOX4 | NADPH oxidase 4 | NOX4 | 1.4 | Similarly nox1 and nox4 were increased at 12 wk and their expression |
| 7891 | NOX4 | NADPH oxidase 4 | nox4 | 1.4 | Similarly nox1 and nox4 were increased at 12 wk and their expression tended to |
| 7891 | NOX4 | NADPH oxidase 4 | nox4 | 1.4 | db db mice at both times reaching statistical significance in nox4 at 12 wk |
| 7889 | NOX1 | NADPH oxidase 1 | nox1 | 0.9 | In the case of nox1 this increase was mostly a consequence of age rather than |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | nox2 | 1.0 | We found no difference in nox2 expression over time or between animals |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.2 | We examined a series of proinflammatory genes including VCAM-1 MCP-1 CTGF OPN and BMP-4 |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | MCP-1 | 1.3 | We examined a series of proinflammatory genes including VCAM-1 MCP-1 CTGF OPN and BMP-4 |
| 2500 | CTGF | connective tissue growth factor | CTGF | 5.3 | We examined a series of proinflammatory genes including VCAM-1 MCP-1 CTGF OPN and BMP-4 |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | OPN | 0.8 | examined a series of proinflammatory genes including VCAM-1 MCP-1 CTGF OPN and BMP-4 |
| 1071 | BMP4 | bone morphogenetic protein 4 | BMP-4 | 2.7 | series of proinflammatory genes including VCAM-1 MCP-1 CTGF OPN and BMP-4 |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.2 | We found no change in VCAM-1 and MCP-1 (not not shown but we observed significant increases |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | MCP-1 | 1.3 | We found no change in VCAM-1 and MCP-1 (not not shown but we observed significant increases in the |
| 2500 | CTGF | connective tissue growth factor | CTGF | 5.3 | in Fig 4 in 4-wk-old db/db db db mice aortic CTGF gene expression was increased compared with that from misty mice |
| 1071 | BMP4 | bone morphogenetic protein 4 | BMP-4 | 2.7 | No changes in BMP-4 or OPN expression were observed at 4 wk |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | OPN | 0.8 | No changes in BMP-4 or OPN expression were observed at 4 wk |
| 2500 | CTGF | connective tissue growth factor | CTGF | 5.3 | aortas from 12-wk-old db/db db db mice the increase in CTGF mRNA was maintained (295.5 295.5 _amp_#177 93.8% P = 0.02 |
| 1071 | BMP4 | bone morphogenetic protein 4 | BMP-4 | 2.7 | was maintained (295.5 295.5 _amp_#177 93.8% P = 0.02 and BMP-4 (230.3 230.3 _amp_#177 50.4% P _lt_ 0.01 and OPN (188 |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | OPN | 0.8 | and BMP-4 (230.3 230.3 _amp_#177 50.4% P _lt_ 0.01 and OPN (188 188 _amp_#177 54.7% P _lt_ 0.01 expression was significantly |
| 1071 | BMP4 | bone morphogenetic protein 4 | BMP-4 | 2.7 | As is shown in Fig 6 A BMP-4 was dramatically upregulated exclusively in response to diabetes progression misty |
| 1071 | BMP4 | bone morphogenetic protein 4 | BMP-4 | 2.7 | to diabetes progression misty mice had no significant increase in BMP-4 expression with age |
| 1071 | BMP4 | bone morphogenetic protein 4 | BMP-4 | 2.7 | mice treated with Tempol showed a significant reduction in aortic BMP-4 protein production as evaluated by Western blot ( Fig 6 |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | OPN | 0.8 | OPN was also ROS sensitive ( Fig 6 C |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | OPN | 0.8 | No OPN expression was detected in misty mice at any time |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | OPN | 0.8 | However aortas from diabetic animals were strikingly positive for OPN in the media and this staining was partially reduced after |
| 2500 | CTGF | connective tissue growth factor | CTGF | 5.3 | In contrast CTGF protein showed a very different pattern of expression from the |
| 2500 | CTGF | connective tissue growth factor | CTGF | 5.3 | CTGF was strongly induced in aortas from both misty and db/db |
| 2500 | CTGF | connective tissue growth factor | CTGF | 5.3 | Of importance CTGF protein and mRNA expression was unaffected by Tempol treatment ( |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | nadph oxidase derived reactive oxygen species ros production and inflammation are potential mediators of dm associated vascular diseases. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | using db/db mice as a type 2 diabetes model we examined the relationship between nadph oxidase derived ros and vascular inflammation. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | when compared with control m +/+ mice aortas from 4 and 12 wk old db/db mice had higher nadph oxidase activity and increased superoxide levels leading to nadph oxidase dependent impaired vasodilation at 12 wk. |
| 1071 | BMP4 | bone morphogenetic protein 4 | bone morphogenetic protein 4 | 1.0 | iabetes progression from 4 to 12 wk led to increased nox1 nox4 and p22 subunit mrnas and induced the expression of a group of matrix remodeling related cytokines: connective tissue growth factor ctgf bone morphogenetic protein 4 bmp 4 and osteopontin opn . |
| 2500 | CTGF | connective tissue growth factor | connective tissue growth factor | 1.0 | diabetes progression from 4 to 12 wk led to increased nox1 nox4 and p22 subunit mrnas and induced the expression of a group of matrix remodeling related cytokines: connective tissue growth factor ctgf bone morphogenetic protein 4 bmp 4 and osteopontin opn . |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | osteopontin | 1.0 | to increased nox1 nox4 and p22 subunit mrnas and induced the expression of a group of matrix remodeling related cytokines: connective tissue growth factor ctgf bone morphogenetic protein 4 bmp 4 and osteopontin opn . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | lammatory disease in which vascular cells and blood derived inflammatory cells participate in a local chronic response through regulation of inflammatory cytokines such as tumor necrosis factor alpha tnf alpha and interleukins 32 . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tumor necrosis factor alpha | 1.0 | atherosclerosis is an inflammatory disease in which vascular cells and blood derived inflammatory cells participate in a local chronic response through regulation of inflammatory cytokines such as tumor necrosis factor alpha tnf alpha and interleukins 32 . |
| 6081 | INS | insulin | insulin | 1.0 | since the discovery that tnf alpha expression also occurs in adipose tissue 21 the contribution of inflammation to diabetes and insulin resistance has been noted. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | since the discovery that tnf alpha expression also occurs in adipose tissue 21 the contribution of inflammation to diabetes and insulin resistance has been noted. |
| 6081 | INS | insulin | insulin | 1.0 | both hyperglycemia and insulin activate nadph oxidases suggesting that these enzymes may be important in type 2 diabetes as well. |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | osteopontin | 1.0 | osteopontin opn a widely distributed acidic phosphoprotein found in atherosclerotic plaques contributes to vascular inflammation by regulating macrophage function vascular smooth muscle cell vsmc proliferation a |
| 1071 | BMP4 | bone morphogenetic protein 4 | bone morphogenetic protein 4 | 1.0 | another important matrix cytokine is bone morphogenetic protein 4 bmp 4 a member of the transforming growth factor beta superfamily which is also upregulated in aortic plaques 8 43 stimulates adhesion molecule expression 43 and causes nadph oxidase dependent endoth |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | s bone morphogenetic protein 4 bmp 4 a member of the transforming growth factor beta superfamily which is also upregulated in aortic plaques 8 43 stimulates adhesion molecule expression 43 and causes nadph oxidase dependent endothelial dysfunction 33 . |
| 3122 | LEFTY2 | left-right determination factor 2 | transforming growth factor beta superfamily | 1.0 | another important matrix cytokine is bone morphogenetic protein 4 bmp 4 a member of the transforming growth factor beta superfamily which is also upregulated in aortic plaques 8 43 stimulates adhesion molecule expression 43 and causes nadph oxidase dependent endothelial dysfunction 33 . |
| 2500 | CTGF | connective tissue growth factor | connective tissue growth factor | 1.0 | finally connective tissue growth factor ctgf is a potent chemotactic and extracellular matrix inducing growth factor found at high levels in atherosclerotic but not in normal vessels 35 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in this study we hypothesized that nadph oxidase activity is increased in a mouse model of type 2 diabetes and metabolic syndrome and that the resulting increase in ros contributes to impaired vasoreactivity and inflammation. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | we found that aortic ros production is higher in diabetic mice and as diabetes progresses nadph oxidase activity and expression increase. |
| 6553 | LEP | leptin | leptin | 1.0 | receptor and misty mice related genotype a / a m +/ m + expressing wild type leptin receptors were purchased from jackson laboratory bar harbor me and bred in house. |
| 6554 | LEPR | leptin receptor | leptin receptor | 1.0 | db/db mice related genotype a / a + lepr /+ lepr a model of type 2 diabetes and the metabolic syndrome harboring a mutation in the leptin receptor and misty mice related genotype a / a m +/ m + expressing wild type leptin receptors were purchased from jackson laboratory bar harbor me and bred in house. |
| 6081 | INS | insulin | insulin | 1.0 | insulin levels were analyzed at yerkes national primate research center atlanta ga using an elisa method alpco diagnostics salem nh . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | to examine the role of ros produced by the nadph oxidase in inhibiting relaxation preconstricted isolated vessels were incubated in the organ chamber with apocynin 0.5 mmol/l for 30 min before dose response curves were performed. |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | mcp 1 | 1.0 | message expression was quantified with the use of the lightcycler instrument roche with sybr green dye and specific mouse nox1 nox2 nox4 p22 vcam 1 mcp 1 ctgf bmp 4 and opn primers table 1 and normalized to 18s ribosomal rna. |
| 6081 | INS | insulin | insulin | 1.0 | glucose and insulin were not significantly elevated at 4 wk in these animals; however their weight was greater and their lipid levels tended to be higher compared with 4 wk old misty mice. |
| 6081 | INS | insulin | insulin | 1.0 | however inflammatory molecules such as tnf alpha can induce insulin resistance 46 and diabetes upregulates inflammatory genes in adipose tissue 49 . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | however inflammatory molecules such as tnf alpha can induce insulin resistance 46 and diabetes upregulates inflammatory genes in adipose tissue 49 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | we found a nadph oxidase dependent reduction in the vasodilatory response to acetylcholine. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | for example in animal models of diabetes type 1 mitochondrial ros are implicated in cardiomyopathy 41 whereas nadph oxidase derived ros are associated with proteinuria and vascular injury 2 47 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in otsuka long evans tokushima fatty rats aortic nadh oxidase activity and gp91 /p22 expression is increased 25 whereas in goto kakizaki rats no increase in aortic nadph oxidase activity is observed 38 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | our study was not designed to discriminate between mitochondria and nadph oxidase derived ros but rather to determine whether nadph oxidases are regulated by the onset of type 2 diabetes. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | we found a significant increase in nadph oxidase activity during the development of diabetes in aortas from db/db mice fig 1 a . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | consistent with a role for nadph oxidases in diabetic vascular dysfunction we found an increase in nadph oxidase expression in aortas from db/db mice fig 1 b . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | however nadph oxidase activity and ros production were significantly increased only as a consequence of diabetes and did not change with age in either misty or db/db mice figs 1 a and 2 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | furthermore the greater increase in nadph oxidase activity compared with o 2 levels in 12 wk old diabetic animals suggests that the age related increase in ros can be compensated perhaps by induction of antioxidant enzymes but that diabetes associat |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | mcp 1 | 1.0 | previous work on inflammatory gene expression in diabetic animals centered on mcp 1 and vcam 1 53 . |
| 613 | APOE | apolipoprotein E | apolipoprotein e | 1.0 | this differs from results reported in db/db mice crossed into the apolipoprotein e deficient background in which vcam 1 tissue factor and matrix metalloproteinase 9 were induced when plaques were present 51 . |
| 7176 | MMP9 | matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) | matrix metalloproteinase 9 | 1.0 | this differs from results reported in db/db mice crossed into the apolipoprotein e deficient background in which vcam 1 tissue factor and matrix metalloproteinase 9 were induced when plaques were present 51 . |
| 6081 | INS | insulin | insulin | 1.0 | 4 showed that in ren 2 overexpressing mice tempol improved the insulin resistance index. |
| 6081 | INS | insulin | insulin | 1.0 | however the ability of tempol to improve the lipid profile hyperglycemia and some inflammatory responses without affecting weight gain or insulin levels indicates that inflammation is not related to insulin or obesity in this model. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | aortic nadph oxidase activity and expression in db/db and misty mice. |
| 1071 | BMP4 | bone morphogenetic protein 4 | bone morphogenetic protein 4 | 1.0 | total rna was purified from db/db and misty aortas and osteopontin connective tissue growth factor ctgf bone morphogenetic protein 4 bmp 4 mrnas were measured using real time pcr and normalized to 18s rrna. |
| 2500 | CTGF | connective tissue growth factor | connective tissue growth factor | 1.0 | total rna was purified from db/db and misty aortas and osteopontin connective tissue growth factor ctgf bone morphogenetic protein 4 bmp 4 mrnas were measured using real time pcr and normalized to 18s rrna. |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | osteopontin | 1.0 | total rna was purified from db/db and misty aortas and osteopontin connective tissue growth factor ctgf bone morphogenetic protein 4 bmp 4 mrnas were measured using real time pcr and normalized to 18s rrna. |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | osteopontin | 1.0 | effect of tempol on osteopontin and bmp 4 expression in aortas from 12 wk old mice. |
| 437 | ALPI | alkaline phosphatase, intestinal | alkaline phosphatase | 1.0 | c : sections were stained for osteopontin using a polyclonal antibody and were visualized with alkaline phosphatase. |
| 11255 | SPP1 | secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) | osteopontin | 1.0 | c : sections were stained for osteopontin using a polyclonal antibody and were visualized with alkaline phosphatase. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | pcr primers used for amplification of cytokine and nadph oxidase genes |
| 437 | ALPI | alkaline phosphatase, intestinal | alkaline phosphatase | 1.0 | for opn a polyclonal antibody was used catalog no 18621 ibl japan and visualized using the avidin biotin complex system/alkaline phosphatase abc kit vector . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | aortic superoxide production and nadph oxidase activity and expression. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | we then studied whether nadph oxidase activation leads to an overall increase in vascular o 2 production. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | thus aortic o 2 production and nadph oxidase expression and activity are increased in db/db mice during diabetes mellitus progression. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | impaired endothelium dependent relaxation is reversed by nadph oxidase inhibition. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | to determine whether this increase in nadph oxidase activity influenced endothelial function we measured endothelium dependent and independent relaxation in aortas in the presence and absence of the nadph oxidase inhibitor apocynin. |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | mcp 1 | 1.0 | we examined a series of proinflammatory genes including vcam 1 mcp 1 ctgf opn and bmp 4. |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | mcp 1 | 1.0 | we found no change in vcam 1 and mcp 1 not shown but we observed significant increases in the latter three genes. |