)| PMID |
16463048 ( ) |
|---|---|
| Title | Gemfibrozil decreases atherosclerosis in experimental diabetes in association with a reduction in oxidative stress and inflammation. |
| Abstract | AIMS/HYPOTHESIS: It is postulated that peroxisome proliferator-activated receptor alpha agonists confer cardiovascular benefits in diabetes, independently of their effects on lipid metabolism. We investigated putative mechanisms responsible for these anti-atherogenic effects in an in vivo model of diabetes-associated atherosclerosis. MATERIALS AND METHODS: Control and streptozotocin-induced diabetic apolipoprotein-deficient mice received gemfibrozil (100 mg kg(-1) day(-1)) or no treatment for 20 weeks. Aortic plaque deposition was assessed by Sudan IV staining and subsequent en face quantification. Superoxide production was measured using lucigenin-enhanced chemiluminescence. Markers of pathways including inflammation and oxidative stress were measured using real-time RT-PCR. RESULTS: No significant effect of gemfibrozil was observed on glycated haemoglobin, cholesterol or insulin in diabetic mice. Diabetes was associated with a three-fold increase in plaque area and a significant increase in NADPH-dependent superoxide compared with control mice. Gemfibrozil significantly attenuated plaque area and superoxide production in diabetic mice. In addition, gemfibrozil reduced the expression of the genes encoding the NADPH oxidase subunits p47phox, gp91phox and Rac-1. In addition, gemfibrozil reduced the expression of the genes encoding nuclear factor kappa B (NF-kappaB) subunit, p65, the NF-kappaB-dependent chemokine monocyte chemoattractant protein-1, and tissue factor. CONCLUSIONS/INTERPRETATIONS: This study demonstrates that gemfibrozil exerts anti-atherogenic actions, independently of changes in cholesterol and glucose metabolism. Such findings emphasise the possible usefulness of fibrates such as gemfibrozil in a setting of atherosclerosis even in the absence of dyslipidaemia. Box 6492, St Kilda Rd Central, Melbourne, 8008, Australia. anna.calkin@baker.edu.au |
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 |
|---|---|---|---|---|
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | 19 | nuclear factor kappa b | NF-kappaB-dependent | |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | 16 | monocyte chemoattractant protein 1 | Ccl2 | mcp 1 | MCP-1 | |
| 7176 | MMP9 | matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) | 13 | mmp9 | MMP9 | Mmp9 | |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | 10 | PPAR | PPARA | |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | 10 | p47phox-dependent | Ncf1 | |
| 320 | AGER | advanced glycosylation end product-specific receptor | 8 | AGER | |
| 6081 | INS | insulin | 8 | insulin | |
| 7166 | MMP2 | matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase) | 7 | Mmp2 | MMP2 | |
| 336 | AGTR1 | angiotensin II receptor, type 1 | 7 | angiotensin ii receptor | AGTR1 | Agtr1 | |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | 6 | Cybb | gp91phox | |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | 6 | nadph oxidase | |
| 9955 | RELA | v-rel reticuloendotheliosis viral oncogene homolog A, nuclear factor of kappa light polypeptide gene enhancer in B-cells 3, p65 (avian) | 6 | Rela | p65 | |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | 5 | Rac-1 | Rac1 | |
| 9958 | REN | renin | 5 | renin | |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | 3 | VCAM1 | Vcam1 | vascular cell adhesion molecule 1 | |
| 613 | APOE | apolipoprotein E | 2 | apolipoprotein e | |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | 1 | p67phox | |
| 6091 | INSR | insulin receptor | 1 | insulin receptor | |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | 1 | intercellular adhesion molecule 1 | |
| 3796 | FOS | v-fos FBJ murine osteosarcoma viral oncogene homolog | 1 | activator protein 1 | |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | 1 | angiotensin ii | |
| 600 | APOA1 | apolipoprotein A-I | 1 | apolipoprotein | |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | 1 | p22phox | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 1.3 | the expression of the genes encoding the NADPH oxidase subunits p47phox gp91phox and Rac-1 |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.3 | expression of the genes encoding the NADPH oxidase subunits p47phox gp91phox and Rac-1 |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | Rac-1 | 0.1 | the genes encoding the NADPH oxidase subunits p47phox gp91phox and Rac-1 |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 1.9 | expression of the genes encoding nuclear factor kappa B (NF-kappaB) NF-kappaB subunit p65 the NF-kappaB-dependent chemokine monocyte chemoattractant protein-1 and tissue |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB-dependent | 2.4 | encoding nuclear factor kappa B (NF-kappaB) NF-kappaB subunit p65 the NF-kappaB-dependent chemokine monocyte chemoattractant protein-1 and tissue factor |
| 9955 | RELA | v-rel reticuloendotheliosis viral oncogene homolog A, nuclear factor of kappa light polypeptide gene enhancer in B-cells 3, p65 (avian) | p65 | 0.2 | the genes encoding nuclear factor kappa B (NF-kappaB) NF-kappaB subunit p65 the NF-kappaB-dependent chemokine monocyte chemoattractant protein-1 and tissue factor |
| 336 | AGTR1 | angiotensin II receptor, type 1 | AGTR1 | 2.2 | Abbreviations AGII angiotensin II -ApoE_amp_#8722 _amp_#8722 apolipoprotein-E-deficient -AGTR1 angiotensin II receptor subtype 1 -GHb glycated haemoglobin -MCP-1 monocyte |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | MCP-1 | 2.3 | apolipoprotein-E-deficient -AGTR1 angiotensin II receptor subtype 1 -GHb glycated haemoglobin -MCP-1 monocyte chemoattractant protein-1 -MMP matrix metalloproteinase -NF-kappaB nuclear factor kappa |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 1.9 | -GHb glycated haemoglobin -MCP-1 monocyte chemoattractant protein-1 -MMP matrix metalloproteinase -NF-kappaB nuclear factor kappa B -PPAR peroxisome proliferator-activated receptor -AGER advanced |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR | 2.7 | chemoattractant protein-1 -MMP matrix metalloproteinase -NF-kappaB nuclear factor kappa B -PPAR peroxisome proliferator-activated receptor -AGER advanced glycation end product-specific receptor -ROS |
| 320 | AGER | advanced glycosylation end product-specific receptor | AGER | 0.9 | metalloproteinase -NF-kappaB nuclear factor kappa B -PPAR peroxisome proliferator-activated receptor -AGER advanced glycation end product-specific receptor -ROS reactive oxygen species |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR | 2.7 | Introduction Fibrates are peroxisome proliferator-activated receptor (PPAR) PPAR A agonists primarily used for the treatment of dyslipidaemia |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPARA | 3.5 | This is supported by studies demonstrating PPARA expression in cells of the vessel wall including endothelial cells |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPARA | 3.5 | In addition polymorphisms in the PPARA gene have been linked to alterations in the risk of |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | Cybb | 1.0 | We demonstrated that diabetes was associated with an upregulation of Cybb (control control vs diabetic p _lt_0.001 Ncf1 (control control vs |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | Ncf1 | 1.0 | an upregulation of Cybb (control control vs diabetic p _lt_0.001 Ncf1 (control control vs diabetic p _lt_0.01 and Rac1 ( p |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.3 | p _lt_0.01 and Rac1 ( p _lt_0.05 the genes encoding gp91phox p47phox and Rac-1 respectively |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 1.3 | _lt_0.01 and Rac1 ( p _lt_0.05 the genes encoding gp91phox p47phox and Rac-1 respectively |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | Rac1 | 0.0 | p _lt_0.001 Ncf1 (control control vs diabetic p _lt_0.01 and Rac1 ( p _lt_0.05 the genes encoding gp91phox p47phox and Rac-1 |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | Rac-1 | 0.1 | Rac1 ( p _lt_0.05 the genes encoding gp91phox p47phox and Rac-1 respectively |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.3 | Expression of b NAD(P)H NAD P H oxidase subunits gp91phox c p47phox and d Rac-1 as quantified by real-time RT-PCR |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 1.3 | of b NAD(P)H NAD P H oxidase subunits gp91phox c p47phox and d Rac-1 as quantified by real-time RT-PCR |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | Rac-1 | 0.0 | NAD P H oxidase subunits gp91phox c p47phox and d Rac-1 as quantified by real-time RT-PCR |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 1.9 | We measured the regulation of nuclear factor kappa B (NF-kappaB), NF-kappaB a mediator of inflammation via gene expression of the NF-kappaB |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 1.9 | NF-kappaB a mediator of inflammation via gene expression of the NF-kappaB subunit Rela |
| 9955 | RELA | v-rel reticuloendotheliosis viral oncogene homolog A, nuclear factor of kappa light polypeptide gene enhancer in B-cells 3, p65 (avian) | Rela | 0.5 | mediator of inflammation via gene expression of the NF-kappaB subunit Rela |
| 9955 | RELA | v-rel reticuloendotheliosis viral oncogene homolog A, nuclear factor of kappa light polypeptide gene enhancer in B-cells 3, p65 (avian) | Rela | 0.5 | Diabetes was associated with an upregulation of the expression of Rela and this was attenuated by gemfibrozil treatment (Table Table 2 |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | Ccl2 | 3.6 | We subsequently investigated the expression of the gene ( Ccl2 encoding the chemokine monocyte chemoattractant protein-1 (MCP-1), MCP-1 an NF-kappaB-dependent |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | MCP-1 | 2.3 | gene ( Ccl2 encoding the chemokine monocyte chemoattractant protein-1 (MCP-1), MCP-1 an NF-kappaB-dependent protein which has been shown to play an |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB-dependent | 2.4 | Ccl2 encoding the chemokine monocyte chemoattractant protein-1 (MCP-1), MCP-1 an NF-kappaB-dependent protein which has been shown to play an important role |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | Ccl2 | 3.6 | We demonstrated an upregulation of Ccl2 gene expression in the aortae of diabetic mice which was |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | Ccl2 | 3.6 | An increase in Ccl2 gene expression may indicate increased macrophage infiltration and thus immunostaining |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | Ccl2 | 3.6 | diabetic mice compared with all other groups consistent with enhanced Ccl2 expression |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM1 | 2.3 | C G control gemfibrozil D G diabetic gemfibrozil VCAM1 vascular cell adhesion molecule-1 |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 1.9 | has also been demonstrated to be under the regulation of NF-kappaB 30 |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | Vcam1 | 2.3 | Whilst we observed a marked increase in Vcam1 gene expression in diabetic mice gemfibrozil did not affect this |
| 336 | AGTR1 | angiotensin II receptor, type 1 | Agtr1 | 2.2 | In the current study we demonstrated a reduction in Agtr1 gene expression in the aortae of both control ( p |
| 320 | AGER | advanced glycosylation end product-specific receptor | AGER | 0.9 | the gene encoding the advanced glycation end product-specific receptor (AGER), AGER was upregulated ( p _lt_0.01 and this was abrogated by |
| 7166 | MMP2 | matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase) | MMP2 | 1.1 | MMPs are involved in degradation of extracellular matrix and both MMP2 and MMP9 have been associated with plaque stability 33 |
| 7176 | MMP9 | matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) | MMP9 | 1.3 | MMPs are involved in degradation of extracellular matrix and both MMP2 and MMP9 have been associated with plaque stability 33 |
| 7176 | MMP9 | matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) | MMP9 | 1.3 | involved in degradation of extracellular matrix and both MMP2 and MMP9 have been associated with plaque stability 33 |
| 7166 | MMP2 | matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase) | Mmp2 | 1.1 | diabetic mice had an upregulation in aortic gene expression of Mmp2 and this was attenuated with gemfibrozil treatment (Table Table 2 |
| 7176 | MMP9 | matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) | Mmp9 | 1.3 | Furthermore whilst diabetes was not associated with an alteration in Mmp9 gene expression gemfibrozil significantly downregulated gene expression of this enzyme |
| 320 | AGER | advanced glycosylation end product-specific receptor | AGER | 0.9 | and mediators of inflammation (2) 2 oxidative stress (3) 3 AGER (4) 4 the renin-angiotensin system and (5) 5 MMPs implicated |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPARA | 3.5 | number of studies have assessed the role of fibrates and PPARA in rodents albeit in a non-diabetic context these studies reported |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPARA | 3.5 | mice demonstrated lower en face atherosclerotic lesions compared with PPARA+/+ PPARA apoE_amp_#8722;/_amp_#8722; apoE_amp_#8722 _amp_#8722 mice 34 |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPARA | 3.5 | independent could not be determined since the genetic deletion of PPARA was associated with higher VLDL levels |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 1.9 | NF-kappaB is a proinflammatory transcription factor which has been demonstrated to |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPAR | 2.7 | PPAR agonists are now thought to mediate many of their anti-inflammatory |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 1.9 | actions via the transrepression pathway interfering with the activation of NF-kappaB and activator protein-1 pathways 39 |
| 9955 | RELA | v-rel reticuloendotheliosis viral oncogene homolog A, nuclear factor of kappa light polypeptide gene enhancer in B-cells 3, p65 (avian) | Rela | 0.5 | confirmed that gemfibrozil treatment is associated with a reduction in Rela gene expression in vivo |
| 336 | AGTR1 | angiotensin II receptor, type 1 | Agtr1 | 2.2 | secondary to an attenuation in the aortic gene expression of Agtr1 as AGII has been reported to be associated with increased |
| 9955 | RELA | v-rel reticuloendotheliosis viral oncogene homolog A, nuclear factor of kappa light polypeptide gene enhancer in B-cells 3, p65 (avian) | Rela | 0.5 | been reported to be associated with increased expression of the Rela subunit of NF-kappaB 32 |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 1.9 | be associated with increased expression of the Rela subunit of NF-kappaB 32 |
| 9955 | RELA | v-rel reticuloendotheliosis viral oncogene homolog A, nuclear factor of kappa light polypeptide gene enhancer in B-cells 3, p65 (avian) | Rela | 0.5 | This effect on Rela expression appears to be biologically relevant since altered expression of |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | Ccl2 | 3.6 | to be biologically relevant since altered expression of the chemokine Ccl2 known to be under the regulation of NF-kappaB 40 was |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 1.9 | the chemokine Ccl2 known to be under the regulation of NF-kappaB 40 was also observed |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | MCP-1 | 2.3 | MCP-1 is a key atherogenic molecule responsible for migration of monocytes |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | MCP-1 | 2.3 | which demonstrated a role for fibrates in the attenuation of MCP-1 expression 6 and suggest that this drug may also downregulate |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB-dependent | 2.4 | 6 and suggest that this drug may also downregulate other NF-kappaB-dependent pro-atherogenic molecules |
| 320 | AGER | advanced glycosylation end product-specific receptor | AGER | 0.9 | Diabetic mice demonstrated an upregulation of AGER as has been shown previously 41 |
| 320 | AGER | advanced glycosylation end product-specific receptor | AGER | 0.9 | The effect of interference with AGER has clearly been demonstrated by Bucciarelli et al. who observed |
| 320 | AGER | advanced glycosylation end product-specific receptor | AGER | 0.9 | al. who observed a marked reduction in atherosclerosis with soluble AGER treatment 24 in association with reductions in inflammation and mononuclear |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 1.9 | however not totally surprising since Ager expression is regulated by NF-kappaB with an NF-kappaB-binding site in its promoter region 42 |
| 320 | AGER | advanced glycosylation end product-specific receptor | AGER | 0.9 | Interestingly the converse is also true with AGER inducing NF-kappaB expression 43 |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 1.9 | Interestingly the converse is also true with AGER inducing NF-kappaB expression 43 |
| 320 | AGER | advanced glycosylation end product-specific receptor | AGER | 0.9 | have demonstrated a reduction in expression of the genes encoding AGER and NF-kappaB and cannot at this stage determine which of |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 1.9 | a reduction in expression of the genes encoding AGER and NF-kappaB and cannot at this stage determine which of these pathways |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPARA | 3.5 | of these pathways is upstream and most closely linked to PPARA agonism |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 1.9 | has also been shown to be under the regulation of NF-kappaB 30 and be upregulated in diabetes a state of increased |
| 7166 | MMP2 | matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase) | MMP2 | 1.1 | Both MMP2 and MMP9 are produced in atherosclerotic plaques and appear to |
| 7176 | MMP9 | matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) | MMP9 | 1.3 | Both MMP2 and MMP9 are produced in atherosclerotic plaques and appear to |
| 7176 | MMP9 | matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) | MMP9 | 1.3 | Both MMP2 and MMP9 are produced in atherosclerotic plaques and appear to localise around |
| 7166 | MMP2 | matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase) | Mmp2 | 1.1 | the current study diabetes was associated with an upregulation of Mmp2 but no change in Mmp9 expression |
| 7176 | MMP9 | matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) | Mmp9 | 1.3 | associated with an upregulation of Mmp2 but no change in Mmp9 expression |
| 7166 | MMP2 | matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase) | Mmp2 | 1.1 | Gemfibrozil abrogated both Mmp2 and Mmp9 gene expression implicating a further role for this |
| 7176 | MMP9 | matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) | MMP9 | 1.3 | Gemfibrozil abrogated both Mmp2 and Mmp9 gene expression implicating a further role for this |
| 7176 | MMP9 | matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) | Mmp9 | 1.3 | Gemfibrozil abrogated both Mmp2 and Mmp9 gene expression implicating a further role for this drug in |
| 9232 | PPARA | peroxisome proliferator-activated receptor alpha | PPARA | 3.5 | Studies in macrophages demonstrate that PPARA activation leads to increased superoxide and hydrogen peroxide production via |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 1.3 | hydrogen peroxide production via an upregulation of NADPH oxidase subunits p47phox p67phox and gp91phox 48 |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67phox | 1.0 | peroxide production via an upregulation of NADPH oxidase subunits p47phox p67phox and gp91phox 48 |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.3 | via an upregulation of NADPH oxidase subunits p47phox p67phox and gp91phox 48 |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 1.3 | studies in endothelial cells demonstrated a decrease in p22phox and p47phox and increased antioxidant expression with fibrate therapy 49 |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 0.1 | Conversely studies in endothelial cells demonstrated a decrease in p22phox and p47phox and increased antioxidant expression with fibrate therapy 49 |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 1.3 | increase in gene expression of various NADPH oxidase subunits including p47phox gp91phox and Rac-1 |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 1.3 | in gene expression of various NADPH oxidase subunits including p47phox gp91phox and Rac-1 |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | Rac-1 | 0.1 | expression of various NADPH oxidase subunits including p47phox gp91phox and Rac-1 |
| 336 | AGTR1 | angiotensin II receptor, type 1 | Agtr1 | 2.2 | had effects on the renin-angiotensin system with a reduction in Agtr1 gene expression in diabetic mice |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 1.3 | particular by activation of NADPH oxidase and more specifically the p47phox subunit of NADPH oxidase 53 |
| 7166 | MMP2 | matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase) | MMP2 | 1.1 | Interestingly a recent study has demonstrated that AGII reduces MMP2 in a p47phox-dependent manner although these studies were performed in |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox-dependent | 1.0 | recent study has demonstrated that AGII reduces MMP2 in a p47phox-dependent manner although these studies were performed in cultured smooth muscle |
| 336 | AGTR1 | angiotensin II receptor, type 1 | Agtr1 | 2.2 | In the current study we observed a reduction in Agtr1 Ncf1 and Mmp2 gene expression |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | Ncf1 | 1.0 | In the current study we observed a reduction in Agtr1 Ncf1 and Mmp2 gene expression |
| 7166 | MMP2 | matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase) | Mmp2 | 1.1 | current study we observed a reduction in Agtr1 Ncf1 and Mmp2 gene expression |
| 336 | AGTR1 | angiotensin II receptor, type 1 | AGTR1 | 2.2 | We postulate that the observed reduction in AGTR1 expression in diabetic mice resulted in a downregulation of AGII-mediated |
| 600 | APOA1 | apolipoprotein A-I | apolipoprotein | 1.0 | materials and methods control and streptozotocin induced diabetic apolipoprotein deficient mice received gemfibrozil 100 mg kg _amp_#8722;1 day _amp_#8722;1 or no treatment for 20 weeks. |
| 6081 | INS | insulin | insulin | 1.0 | results no significant effect of gemfibrozil was observed on glycated haemoglobin cholesterol or insulin in diabetic mice. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in addition gemfibrozil reduced the expression of the genes encoding the nadph oxidase subunits p47phox gp91phox and rac 1. |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | nuclear factor kappa b | 1.0 | in addition gemfibrozil reduced the expression of the genes encoding nuclear factor kappa b nf kappab subunit p65 the nf kappab dependent chemokine monocyte chemoattractant protein 1 and tissue factor. |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | monocyte chemoattractant protein 1 | 1.0 | in addition gemfibrozil reduced the expression of the genes encoding nuclear factor kappa b nf kappab subunit p65 the nf kappab dependent chemokine monocyte chemoattractant protein 1 and tissue factor. |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | nuclear factor kappa b | 1.0 | apoe_amp_#8722;/_amp_#8722; apolipoprotein e deficient agtr1 angiotensin ii receptor subtype 1 ghb glycated haemoglobin mcp 1 monocyte chemoattractant protein 1 mmp matrix metalloproteinase nf kappab nuclear factor kappa b ppar peroxisome proliferator activated receptor ager advanced glycation end product specific receptor ros reactive oxygen species |
| 613 | APOE | apolipoprotein E | apolipoprotein e | 1.0 | abbreviations agii angiotensin ii apoe_amp_#8722;/_amp_#8722; apolipoprotein e deficient agtr1 angiotensin ii receptor subtype 1 ghb glycated haemoglobin mcp 1 monocyte chemoattractant protein 1 mmp matrix metalloproteinase nf kappab nuclear factor kappa b ppar peroxisome proli |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | mcp 1 | 1.0 | abbreviations agii angiotensin ii apoe_amp_#8722;/_amp_#8722; apolipoprotein e deficient agtr1 angiotensin ii receptor subtype 1 ghb glycated haemoglobin mcp 1 monocyte chemoattractant protein 1 mmp matrix metalloproteinase nf kappab nuclear factor kappa b ppar peroxisome proliferator activated receptor ager advanced glycation end product specific receptor |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | monocyte chemoattractant protein 1 | 1.0 | abbreviations agii angiotensin ii apoe_amp_#8722;/_amp_#8722; apolipoprotein e deficient agtr1 angiotensin ii receptor subtype 1 ghb glycated haemoglobin mcp 1 monocyte chemoattractant protein 1 mmp matrix metalloproteinase nf kappab nuclear factor kappa b ppar peroxisome proliferator activated receptor ager advanced glycation end product specific receptor ros reactive oxygen species |
| 336 | AGTR1 | angiotensin II receptor, type 1 | angiotensin ii receptor | 1.0 | abbreviations agii angiotensin ii apoe_amp_#8722;/_amp_#8722; apolipoprotein e deficient agtr1 angiotensin ii receptor subtype 1 ghb glycated haemoglobin mcp 1 monocyte chemoattractant protein 1 mmp matrix metalloproteinase nf kappab nuclear factor kappa b ppar peroxisome proliferator activated receptor ager advanced |
| 9958 | REN | renin | renin | 1.0 | furthermore diabetes is associated with an upregulation of the renin angiotensin system [ 20 ] advanced glycation endproducts [ 21 ] and oxidative stress [ 22 ] all of which have been shown to contribute towards the development and progression of atherosclerosis. |
| 613 | APOE | apolipoprotein E | apolipoprotein e | 1.0 | the apolipoprotein e deficient apoe_amp_#8722;/_amp_#8722; mouse is a commonly used rodent model of atherosclerosis. |
| 9958 | REN | renin | renin | 1.0 | this model has been used to assess the role of the renin angiotensin system [ 20 23 ] the advanced glycation pathway [ 24 ] and growth factors [ 25 ] on diabetes associated atherosclerosis. |
| 6081 | INS | insulin | insulin | 1.0 | fasting insulin was measured by an ria kit linco research st charles mi usa; intra and intervariability [cv] were 4.8 and 7.4% respectively . |
| 6081 | INS | insulin | insulin | 1.0 | diabetic mice had increased plasma glucose and ghb and decreased plasma insulin concentrations compared with control mice. |
| 6081 | INS | insulin | insulin | 1.0 | in control mice gemfibrozil significantly reduced ghb and insulin levels and ldl cholesterol. |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | nuclear factor kappa b | 1.0 | we measured the regulation of nuclear factor kappa b nf kappab a mediator of inflammation via gene expression of the nf kappab subunit rela . |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | mcp 1 | 1.0 | we subsequently investigated the expression of the gene ccl2 encoding the chemokine monocyte chemoattractant protein 1 mcp 1 an nf kappab dependent protein which has been shown to play an important role in the initial stages of plaque development [ 29 ]. |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | monocyte chemoattractant protein 1 | 1.0 | we subsequently investigated the expression of the gene ccl2 encoding the chemokine monocyte chemoattractant protein 1 mcp 1 an nf kappab dependent protein which has been shown to play an important role in the initial stages of plaque development [ 29 ]. |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | vascular cell adhesion molecule 1 | 1.0 | c+g control+gemfibrozil; d+g diabetic+gemfibrozil; vcam1 vascular cell adhesion molecule 1 |
| 9958 | REN | renin | renin | 1.0 | renin angiotensin system angiotensin ii agii has been shown to exert effects on both inflammation and oxidative stress via the agii receptor subtype 1 [ 31 32 ]. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | angiotensin ii | 1.0 | renin angiotensin system angiotensin ii agii has been shown to exert effects on both inflammation and oxidative stress via the agii receptor subtype 1 [ 31 32 ]. |
| 7176 | MMP9 | matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) | mmp9 | 1.0 | markers of plaque stability matrix metalloproteinases mmps are involved in degradation of extracellular matrix and both mmp2 and mmp9 have been associated with plaque stability [ 33 ]. |
| 7176 | MMP9 | matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) | mmp9 | 1.0 | furthermore whilst diabetes was not associated with an alteration in mmp9 gene expression gemfibrozil significantly downregulated gene expression of this enzyme in diabetic mice p _lt_0.05; table 2 . |
| 9958 | REN | renin | renin | 1.0 | indeed in aortae from our diabetic mice gemfibrozil treatment was associated with changes in: 1 various markers and mediators of inflammation; 2 oxidative stress; 3 ager; 4 the renin angiotensin system; and 5 mmps implicated in plaque stability. |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | intercellular adhesion molecule 1 | 1.0 | okapcova and gabor demonstrated reductions in soluble vascular cell and intercellular adhesion molecule 1 and soluble e selectin which were not correlated with lipid profile in the presence or absence of diabetes [ 38 ]. |
| 3796 | FOS | v-fos FBJ murine osteosarcoma viral oncogene homolog | activator protein 1 | 1.0 | ppar agonists are now thought to mediate many of their anti inflammatory actions via the transrepression pathway interfering with the activation of nf kappab and activator protein 1 pathways [ 39 ]. |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | mcp 1 | 1.0 | mcp 1 is a key atherogenic molecule responsible for migration of monocytes to the intima [ 29 ] and indeed we observed fewer macrophages in the vessel wall of gemfibrozil treated mice. |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | mcp 1 | 1.0 | our findings confirm previous studies in endothelial cells which demonstrated a role for fibrates in the attenuation of mcp 1 expression [ 6 ] and suggest that this drug may also downregulate other nf kappab dependent pro atherogenic molecules. |
| 7176 | MMP9 | matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) | mmp9 | 1.0 | both mmp2 and mmp9 are produced in atherosclerotic plaques and appear to localise around the shoulder region of the plaque [ 33 ]. |
| 7176 | MMP9 | matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) | mmp9 | 1.0 | in the current study diabetes was associated with an upregulation of mmp2 but no change in mmp9 expression. |
| 7176 | MMP9 | matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase) | mmp9 | 1.0 | gemfibrozil abrogated both mmp2 and mmp9 gene expression implicating a further role for this drug in improving plaque stability. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | superoxide generated from nadph oxidase appears to be the most abundant form of reactive oxygen species ros in the vessel wall although other ros formed include hydrogen peroxide peroxynitrite and nitrotyrosine [ 46 ]. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | studies in macrophages demonstrate that ppara activation leads to increased superoxide and hydrogen peroxide production via an upregulation of nadph oxidase subunits p47phox p67phox and gp91phox [ 48 ]. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | gemfibrozil significantly attenuated superoxide production in both control and diabetic mice furthermore gemfibrozil abrogated the diabetes induced increase in gene expression of various nadph oxidase subunits including p47phox gp91phox and rac 1. |
| 9958 | REN | renin | renin | 1.0 | gemfibrozil treatment also had effects on the renin angiotensin system with a reduction in agtr1 gene expression in diabetic mice. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | agii is widely recognised to increase the production of ros and in particular to enhance nadph oxidase activity [ 52 ]. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | furthermore ros can activate mmps in particular by activation of nadph oxidase and more specifically the p47phox subunit of nadph oxidase [ 53 ]. |
| 6081 | INS | insulin | insulin | 1.0 | in diabetic mice gemfibrozil had no effect on glucose ghb or insulin levels. |
| 6081 | INS | insulin | insulin | 1.0 | in control mice however gemfibrozil treatment resulted in a reduction in ghb and insulin levels. |
| 6081 | INS | insulin | insulin | 1.0 | both animal [ 54 55 ] and clinical studies [ 56 ] have reported an insulin sensitising effect of fibrate therapy which they attribute to a reduction in lipids. |
| 6091 | INSR | insulin receptor | insulin receptor | 1.0 | moreover ide and co workers demonstrated that fibrates can regulate the insulin receptor signalling pathway [ 57 ]. |
| 6081 | INS | insulin | insulin | 1.0 | it is possible that in contrast to the control mice gemfibrozil had no effect on glycaemic control in diabetic mice since this is a state of insulin deficiency with less opportunity for the potential insulin sensitising effects of the fibrate to be operative. |