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PMID	18539754 ( )
Title	AGE/RAGE produces endothelial dysfunction in coronary arterioles in type 2 diabetic mice.
Abstract	We hypothesized that impaired nitric oxide (NO)-dependent dilation (endothelial dysfunction) in type 2 diabetes results, in part, from elevated production of superoxide (O(2)(*-)) induced by the interaction of advanced glycation end products (AGE)/receptor for AGE (RAGE) and TNF-alpha signaling. We assessed the role of AGE/RAGE and TNF-alpha signaling in endothelial dysfunction in type 2 diabetic (Lepr(db)) mice by evaluation of endothelial function in isolated coronary resistance vessels of normal control (nondiabetic, m Lepr(db)) and diabetic mice. Although dilation of vessels to the endothelium-independent vasodilator sodium nitroprusside (SNP) was not different between diabetic and control mice, dilation to the endothelium-dependent agonist acetylcholine (ACh) was reduced in diabetic vs. control mice. The activation of RAGE with RAGE agonist S100b eliminated SNP-potentiated dilation to ACh in Lepr(db) mice. Administration of a soluble form of RAGE (sRAGE) partially restored dilation in diabetic mice but did not affect dilation in control mice. The expression of RAGE in coronary arterioles was markedly increased in diabetic vs. control mice. We also observed in diabetic mice that augmented RAGE signaling augmented expression of TNF-alpha, because this increase was attenuated by sRAGE or NF-kappaB inhibitor MG132. Protein and mRNA expression of NAD(P)H oxidase subunits including NOX-2, p22(phox), and p40(phox) increased in diabetic compared with control mice. sRAGE significantly inhibited the expression of NAD(P)H oxidase in diabetic mice. These results indicate that AGE/RAGE signaling plays a pivotal role in regulating the production/expression of TNF-alpha, oxidative stress, and endothelial dysfunction in type 2 diabetes.

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Targets by SciMiner Summary

HUGO ID	Symbol	Target Name	#Occur	ActualStr
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	121	tumor necrosis factor alpha \| TNF-alpha \| tnf alpha \|
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	28	NF-kappaB-induced \|
6554	LEPR	leptin receptor	16	leptin receptor \| Lepr \|
10500	S100B	S100 calcium binding protein B	12	S100b \| S100 \|
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	6	NOX-2 \|
7662	NCF4	neutrophil cytosolic factor 4, 40kDa	6	p40 \|
2577	CYBA	cytochrome b-245, alpha polypeptide	6	p22 \|
6081	INS	insulin	4	insulin \|
7661	NCF2	neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2)	2	p67 \|
12663	VCAM1	vascular cell adhesion molecule 1	2	vascular cell adhesion molecule 1 \| VCAM-1 \|
6018	IL6	interleukin 6 (interferon, beta 2)	2	IL-6 \| il 6 \|
7660	NCF1	neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)	2	p47 \|
7889	NOX1	NADPH oxidase 1	2	NOX-1 \|
7891	NOX4	NADPH oxidase 4	2	NOX-4 \|
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	1	nitric oxide synthase \|
11916	TNFRSF1A	tumor necrosis factor receptor superfamily, member 1A	1	TNFR \|
4983	HMGB1	high-mobility group box 1	1	amphoterin \|
4827	HBB	hemoglobin, beta	1	hemoglobin \|
7872	NOS1	nitric oxide synthase 1 (neuronal)	1	NOS \|

Targets by SciMiner Full list

HUGO ID	Symbol	Name	ActualStr	Score	FlankingText
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	end products (AGE)/receptor AGE receptor for AGE (RAGE) RAGE and TNF-alpha signaling
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	We assessed the role of AGE/RAGE AGE RAGE and TNF-alpha signaling in endothelial dysfunction in Type 2 diabetic (Lepr Lepr
6554	LEPR	leptin receptor	Lepr	1.3	TNF-alpha signaling in endothelial dysfunction in Type 2 diabetic (Lepr Lepr mice by evaluation of endothelial function in isolated coronary resistance
6554	LEPR	leptin receptor	Lepr	1.3	isolated coronary resistance vessels of normal control (nondiabetic, nondiabetic m Lepr and diabetic mice
10500	S100B	S100 calcium binding protein B	S100b	0.8	The activation of RAGE with RAGE agonist S100b eliminated SNP-potentiated dilation to ACh in Lepr mice
6554	LEPR	leptin receptor	Lepr	1.3	with RAGE agonist S100b eliminated SNP-potentiated dilation to ACh in Lepr mice
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	in diabetic mice that augmented RAGE signaling augmented expression of TNF-alpha because this increase was attenuated by sRAGE or NF-kappaB inhibitor
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.6	of TNF-alpha because this increase was attenuated by sRAGE or NF-kappaB inhibitor MG132
7662	NCF4	neutrophil cytosolic factor 4, 40kDa	p40	0.3	NAD(P)H NAD P H oxidase subunits including NOX-2 p22 and p40 increased in diabetic compared with control mice sRAGE significantly inhibited
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	NOX-2	0.0	mRNA expression of NAD(P)H NAD P H oxidase subunits including NOX-2 p22 and p40 increased in diabetic compared with control mice
2577	CYBA	cytochrome b-245, alpha polypeptide	p22	0.0	expression of NAD(P)H NAD P H oxidase subunits including NOX-2 p22 and p40 increased in diabetic compared with control mice sRAGE
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	a pivotal role in regulating the production/expression production expression of TNF-alpha oxidative stress and endothelial dysfunction in Type 2 diabetes
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	10 19 29 that the inflammatory cytokine tumor necrosis factor-alpha TNF-alpha plays a pivotal role in endothelial dysfunction the neutralizing antibody
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	a pivotal role in endothelial dysfunction the neutralizing antibody to TNF-alpha restored blunted dilation in diabetic rats ( 19 and diabetic
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	in diabetic rats ( 19 and diabetic mice null for TNF-alpha did not show endothelial dysfunction ( 10
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	TNF-alpha also affects intracellular insulin signaling in fat skeletal muscle and
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	We found that TNF-alpha contributes to oxidative stress in diabetes which may explain in
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	both directly and by regulating the production and expression of TNF-alpha in Type 2 diabetes
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.6	latter proposition is based on observations showing that nuclear factor-kappaB NF-kappaB a transcription factor activated by inflammation and oxidative stress plays
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	by inflammation and oxidative stress plays a key role in TNF-alpha expression
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	Accordingly we evaluated the expression of AGE/RAGE AGE RAGE and TNF-alpha in coronary arterioles in Type 2 diabetic and normal control
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	We also tested whether AGE/RAGE AGE RAGE signaling leads to TNF-alpha expression and production in diabetes
6554	LEPR	leptin receptor	Lepr	1.3	Heterozygote controls (m m Lepr wild-type (WT) WT controls homozygote Type 2 diabetes (Lepr Lepr
6554	LEPR	leptin receptor	Lepr	1.3	Lepr wild-type (WT) WT controls homozygote Type 2 diabetes (Lepr Lepr diabetic and Lepr null for TNF-alpha (db db /db db
6554	LEPR	leptin receptor	Lepr	1.3	WT controls homozygote Type 2 diabetes (Lepr Lepr diabetic and Lepr null for TNF-alpha (db db /db db mice were purchased
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	Type 2 diabetes (Lepr Lepr diabetic and Lepr null for TNF-alpha (db db /db db mice were purchased from Jackson Laboratory
6554	LEPR	leptin receptor	Lepr	1.3	Our studies utilized 12- to 16-wk-old 15- to 25-g m Lepr and WT mice and 25- to 50-g Lepr and db
6554	LEPR	leptin receptor	Lepr	1.3	25-g m Lepr and WT mice and 25- to 50-g Lepr and db /db db mice of either sex
6554	LEPR	leptin receptor	Lepr	1.3	We used the same strain (C57BL/6J) C57BL 6J of m Lepr and db /db db mice to match the backgrounds of
6554	LEPR	leptin receptor	Lepr	1.3	and db /db db mice to match the backgrounds of Lepr mice
6554	LEPR	leptin receptor	Lepr	1.3	The obese mice from the second round of breeding of Lepr and TNF were used in experimentation
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF	3.0	mice from the second round of breeding of Lepr and TNF were used in experimentation
6554	LEPR	leptin receptor	Lepr	1.3	We defined m Lepr and WT mice as controls in this study because the
6554	LEPR	leptin receptor	Lepr	1.3	as controls in this study because the results from m Lepr and WT mice were identical
6554	LEPR	leptin receptor	Lepr	1.3	The Type 2 diabetic Lepr mouse is designated as the diabetic mouse in this study
4827	HBB	hemoglobin, beta	hemoglobin	0.3	(BP) BP were described in detail previously ( 10 and hemoglobin A1c (HbA1c) HbA1c level the index of AGE accumulation was
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	Treatment with TNF-alpha neutralization soluble RAGE and MG132
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	The neutralizing antibody to TNF-alpha (anti-TNF) anti-TNF ( 10 was 2E2 monoclonal antibody (2E2 2E2
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	ip 3 days dosage was based on our estimates of TNF-alpha expression (in in the low nanogram or picogram range and
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	for 10 days to determine the interaction between RAGE and TNF-alpha in Type 2 diabetes and to determine whether RAGE affects
10500	S100B	S100 calcium binding protein B	S100b	0.8	to ACh before and after treatment with the RAGE agonist S100b (10 10 microg/ml, microg ml 60-min extraluminal incubation in the
7662	NCF4	neutrophil cytosolic factor 4, 40kDa	p40	0.3	of RAGE and NAD(P)H NAD P H oxidase subunits p22 p40 p47 p67 NOX-1 NOX-2 (gp91 gp91 and NOX-4 were designed
7660	NCF1	neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)	p47	0.6	RAGE and NAD(P)H NAD P H oxidase subunits p22 p40 p47 p67 NOX-1 NOX-2 (gp91 gp91 and NOX-4 were designed (primer
7661	NCF2	neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2)	p67	0.3	and NAD(P)H NAD P H oxidase subunits p22 p40 p47 p67 NOX-1 NOX-2 (gp91 gp91 and NOX-4 were designed (primer primer
7889	NOX1	NADPH oxidase 1	NOX-1	1.4	NAD(P)H NAD P H oxidase subunits p22 p40 p47 p67 NOX-1 NOX-2 (gp91 gp91 and NOX-4 were designed (primer primer 3
7891	NOX4	NADPH oxidase 4	NOX-4	0.9	subunits p22 p40 p47 p67 NOX-1 NOX-2 (gp91 gp91 and NOX-4 were designed (primer primer 3 software and synthesized (Qiagen) Qiagen
2577	CYBA	cytochrome b-245, alpha polypeptide	p22	0.1	primers of RAGE and NAD(P)H NAD P H oxidase subunits p22 p40 p47 p67 NOX-1 NOX-2 (gp91 gp91 and NOX-4 were
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	NOX-2	0.2	NAD P H oxidase subunits p22 p40 p47 p67 NOX-1 NOX-2 (gp91 gp91 and NOX-4 were designed (primer primer 3 software
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	Protein expression of RAGE TNF-alpha and NF-kappaB by Western blot analyses
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.6	Protein expression of RAGE TNF-alpha and NF-kappaB by Western blot analyses
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	RAGE TNF-alpha and NF-kappaB protein expression were detected by Western blot analysis
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.6	RAGE TNF-alpha and NF-kappaB protein expression were detected by Western blot analysis with the
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	were detected by Western blot analysis with the use of TNF-alpha primary antibodies (Santa Santa Cruz or RAGE or NF-kappaB primary
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.6	of TNF-alpha primary antibodies (Santa Santa Cruz or RAGE or NF-kappaB primary antibody (Abcam) Abcam in control mice diabetic mice diabetic
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.6	_amp_#183 day ip 10 days and diabetic mice treated with NF-kappaB inhibitor MG132 (10 10 mg_amp_#183 kg _amp_#183 day ip 5
10500	S100B	S100 calcium binding protein B	S100b	0.8	ACh SNP TEMPOL aminoguanidine and S100b were dissolved in physiological salt solution (PSS) PSS for molecular
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	Our findings support the concept that AGE/RAGE AGE RAGE and TNF-alpha signaling is key to the production of ROS then AGE/RAGE
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	to the production of ROS then AGE/RAGE AGE RAGE and TNF-alpha signaling interact to amplify the oxidative stress and induce endothelial
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	Role of TNF-alpha and AGE/RAGE AGE RAGE signaling in Type 2 diabetes
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.6	proinflammatory and procoagulant cellular responses resulting from the activation of NF-kappaB including the expression of vascular cell adhesion molecule-1 (VCAM-1), VCAM-1
12663	VCAM1	vascular cell adhesion molecule 1	VCAM-1	2.8	NF-kappaB including the expression of vascular cell adhesion molecule-1 (VCAM-1), VCAM-1 TNF-alpha IL-6 and tissue factor (TF) TF ( 24
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	including the expression of vascular cell adhesion molecule-1 (VCAM-1), VCAM-1 TNF-alpha IL-6 and tissue factor (TF) TF ( 24
6018	IL6	interleukin 6 (interferon, beta 2)	IL-6	0.1	the expression of vascular cell adhesion molecule-1 (VCAM-1), VCAM-1 TNF-alpha IL-6 and tissue factor (TF) TF ( 24
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB-induced	0.6	production of ROS which can stimulate the cascade leading to NF-kappaB-induced transcriptional events
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.6	NF-kappaB will induce expression of TNF-alpha ( 5 23
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	NF-kappaB will induce expression of TNF-alpha ( 5 23
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	Accordingly we determined whether AGE/RAGE AGE RAGE signaling leads to TNF-alpha expression and production in diabetes
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	Our results showed that protein expression of RAGE TNF-alpha and NF-kappaB was elevated in Type 2 diabetes
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.6	Our results showed that protein expression of RAGE TNF-alpha and NF-kappaB was elevated in Type 2 diabetes
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	In Type 2 diabetic mice neutralizing antibody to TNF-alpha the free radical scavenger TEMPOL sRAGE (to to corrupt AGE/RAGE
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.6	sRAGE (to to corrupt AGE/RAGE AGE RAGE signaling or the NF-kappaB inhibitor MG132 decreased the protein expression of RAGE but sRAGE
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	protein expression of RAGE but sRAGE and MG132 also attenuated TNF-alpha expression
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	the evidence for the interaction of AGE/RAGE AGE RAGE with TNF-alpha which may then stimulate the production of O 2 via
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.6	which may then stimulate the production of O 2 via NF-kappaB in Type 2 diabetes
10500	S100B	S100 calcium binding protein B	S100b	0.8	abolished after incubation with both SNP and the RAGE agonist S100b
10500	S100B	S100 calcium binding protein B	S100	0.8	the vessel at least in part via accumulation of S100/calgranulins S100 calgranulins and amphoterin released from activated inflammatory cells provides a
6554	LEPR	leptin receptor	Lepr	1.3	endothelial function was better in db /db db and in Lepr mice treated with anti-TNF or sRAGE
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	impaired vasodilation may result from increased expression/production expression production of TNF-alpha and AGE/RAGE AGE RAGE signaling in Type 2 diabetes
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	TNF-alpha produces a rapid inhibitory action on NO in the endothelium
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	ceramide signaling pathway this mechanism purportedly mediates 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	2.7	We found elevations of TNF-alpha expression in diabetic mice sRAGE decreased TNF-alpha expression in diabetic
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	found elevations of TNF-alpha expression in diabetic mice sRAGE decreased TNF-alpha expression in diabetic mice but did not affect TNF-alpha expression
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	decreased TNF-alpha expression in diabetic mice but did not affect TNF-alpha expression in control mice
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	The exact reason why TNF-alpha is elevated_amp_#8212 obesity diabetes hyperlipidemia or some or all of
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	role of AGE/RAGE AGE RAGE signaling in the expression of TNF-alpha to better understand signaling mechanisms responsible for TNF-alpha expression
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	expression of TNF-alpha to better understand signaling mechanisms responsible for TNF-alpha expression
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	AGE RAGE signaling plays a pivotal role in regulation of TNF-alpha expression
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	Furthermore sRAGE decreased TNF-alpha protein expression in diabetic mice ( 10
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	Our results support the concept that the interaction of TNF-alpha with AGE/RAGE AGE RAGE contributes to endothelial dysfunction in diabetic
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.6	The key target of RAGE signaling is NF-kappaB causing pathological changes in gene expression ( 3 25 28
7872	NOS1	nitric oxide synthase 1 (neuronal)	NOS	1.2	may decrease NO availability by decreasing nitric oxide synthase (NOS) NOS activity ( 4
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	our previous study ( 10 we confirmed the links among TNF-alpha NAD(P)H NAD P H oxidase ROS and impaired vasodilation in
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	AGE/RAGE AGE RAGE appear to sum with TNF-alpha to induce the endothelial dysfunction in Type 2 diabetes
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.6	High expression of AGE RAGE and NF-kappaB in lacrimal glands of diabetic rats ( 1 suggests that
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.6	oxidative stress and leads to activation of the transcription factor NF-kappaB ( 5 7
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	Because TNF-alpha has four NF-kappaB sites in its promoter we postulate that
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.6	Because TNF-alpha has four NF-kappaB sites in its promoter we postulate that AGE/RAGE AGE RAGE
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	its promoter we postulate that AGE/RAGE AGE RAGE signaling increases TNF-alpha expression
7662	NCF4	neutrophil cytosolic factor 4, 40kDa	p40	0.3	NAD(P)H NAD P H oxidase subunits (NOX-2, NOX-2 p22 and p40 and NAD(P)H NAD P H oxidase activity were significantly higher
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	NOX-2	0.0	and protein of NAD(P)H NAD P H oxidase subunits (NOX-2, NOX-2 p22 and p40 and NAD(P)H NAD P H oxidase activity
2577	CYBA	cytochrome b-245, alpha polypeptide	p22	0.0	protein of NAD(P)H NAD P H oxidase subunits (NOX-2, NOX-2 p22 and p40 and NAD(P)H NAD P H oxidase activity were
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	to the production of ROS is AGE/RAGE AGE RAGE and TNF-alpha signaling
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	have shown interactions among oxidative stress AGE/RAGE, AGE RAGE and TNF-alpha because oxidative stress induces NF-kappaB and this transcription factor induced
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.6	stress AGE/RAGE, AGE RAGE and TNF-alpha because oxidative stress induces NF-kappaB and this transcription factor induced both RAGE and TNF-alpha expression
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	induces NF-kappaB and this transcription factor induced both RAGE and TNF-alpha expression and TNF-alpha induced RAGE expression ( Fig 7
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	this transcription factor induced both RAGE and TNF-alpha expression and TNF-alpha induced RAGE expression ( Fig 7
10500	S100B	S100 calcium binding protein B	S100b	0.8	with sodium nitroprusside (SNP) SNP alone or both SNP and S100b was identical to control ( n = 6
10500	S100B	S100 calcium binding protein B	S100b	0.8	to ACh was abolished after incubation with both SNP and S100b (diabetic+SNP diabetic SNP vs diabetic SNP S100b n = 9
10500	S100B	S100 calcium binding protein B	S100b	0.8	both SNP and S100b (diabetic+SNP diabetic SNP vs diabetic SNP S100b n = 9 * P _lt_ 0.05 vs diabetic #
10500	S100B	S100 calcium binding protein B	S100b	0.8	0.05 vs diabetic # P _lt_ 0.05 vs diabetic SNP S100b
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.6	was higher in diabetic mice but sRAGE or nuclear factor-kappaB NF-kappaB inhibitor MG132 decreased NAD(P)H NAD P H oxidase activity in
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.6	with anti-TNF or TEMPOL ( A or sRAGE or MG132 NF-kappaB inhibitor ( B
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	Western blot analysis for TNF-alpha protein expression ( A and B and NF-kappaB protein expression
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.6	analysis for TNF-alpha protein expression ( A and B and NF-kappaB protein expression ( C
7662	NCF4	neutrophil cytosolic factor 4, 40kDa	p40	0.3	H oxidase subunit NOX-2 (gp91 gp91 A p22 ( B p40 ( C mRNA expression (expressed expressed as % of control
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	NOX-2	0.0	Real-time PCR analysis for NAD(P)H NAD P H oxidase subunit NOX-2 (gp91 gp91 A p22 ( B p40 ( C mRNA
2577	CYBA	cytochrome b-245, alpha polypeptide	p22	0.0	NAD(P)H NAD P H oxidase subunit NOX-2 (gp91 gp91 A p22 ( B p40 ( C mRNA expression (expressed expressed as
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	Schematic figure showing the interactions among TNF-alpha AGE/RAGE, AGE RAGE and NF-kappaB signaling
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.6	figure showing the interactions among TNF-alpha AGE/RAGE, AGE RAGE and NF-kappaB signaling
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.6	production of reactive oxygen species (ROS), ROS and this induces NF-kappaB activation
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	to the production of ROS is AGE/RAGE AGE RAGE and TNF-alpha signaling
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	have shown interactions among oxidative stress AGE/RAGE, AGE RAGE and TNF-alpha because oxidative stress induces NF-kappaB this transcription factor can induce
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.6	stress AGE/RAGE, AGE RAGE and TNF-alpha because oxidative stress induces NF-kappaB this transcription factor can induce both RAGE and TNF-alpha expression
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	induces NF-kappaB this transcription factor can induce both RAGE and TNF-alpha expression and TNF-alpha can induce RAGE expression
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	transcription factor can induce both RAGE and TNF-alpha expression and TNF-alpha can induce RAGE expression
11916	TNFRSF1A	tumor necrosis factor receptor superfamily, member 1A	TNFR	1.2	EC endothelial cells VSMCs vascular smooth muscle cells TNFR TNF-alpha receptor
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	EC endothelial cells VSMCs vascular smooth muscle cells TNFR TNF-alpha receptor
10500	S100B	S100 calcium binding protein B	S100b	0.8	(0.1 0.1 microM and after incubation of the vessels with S100b in the presence of SNP (0.1 0.1 microM
10500	S100B	S100 calcium binding protein B	S100b	0.8	(0.1 0.1 microM and after incubation of the vessels with S100b in the presence of SNP (0.1 0.1 microM
10500	S100B	S100 calcium binding protein B	S100b	0.8	Nonetheless activation of RAGE with S100b eliminated this effect
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.6	and diabetic mice treated with sRAGE or MG132 sRAGE and NF-kappaB inhibitor MG132 decreased NAD(P)H NAD P H oxidase activity in
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	Protein expression of TNF-alpha and NF-kappaB in isolated coronary arterioles
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.6	Protein expression of TNF-alpha and NF-kappaB in isolated coronary arterioles
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	TNF-alpha expression ( Fig 5 A and B was elevated over
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.6	Fig 5 A and B was elevated over twofold and NF-kappaB expression ( Fig 5 C was elevated about fourfold in
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	elevated about fourfold in diabetic mice sRAGE or MG132 decreased TNF-alpha and NF-kappaB expression in diabetic mice but did not affect
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.6	fourfold in diabetic mice sRAGE or MG132 decreased TNF-alpha and NF-kappaB expression in diabetic mice but did not affect expression in
7794	NFKB1	nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)	NF-kappaB	0.6	NF-kappaB expression was similar in db /db db mice and control
7662	NCF4	neutrophil cytosolic factor 4, 40kDa	p40	0.3	for NAD(P)H NAD P H oxidase (NOX-2, NOX-2 p22 and p40 was higher in diabetic mice than in control mice mRNA
7660	NCF1	neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1)	p47	0.6	in diabetic mice than in control mice mRNA expression of p47 p67 NOX-1 and NOX-4 (data data not shown was similar
7661	NCF2	neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2)	p67	0.3	diabetic mice than in control mice mRNA expression of p47 p67 NOX-1 and NOX-4 (data data not shown was similar in
7889	NOX1	NADPH oxidase 1	NOX-1	1.4	mice than in control mice mRNA expression of p47 p67 NOX-1 and NOX-4 (data data not shown was similar in diabetic
7891	NOX4	NADPH oxidase 4	NOX-4	0.9	in control mice mRNA expression of p47 p67 NOX-1 and NOX-4 (data data not shown was similar in diabetic and control
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	NOX-2	0.0	( Fig 6 for NAD(P)H NAD P H oxidase (NOX-2, NOX-2 p22 and p40 was higher in diabetic mice than in
2577	CYBA	cytochrome b-245, alpha polypeptide	p22	0.0	Fig 6 for NAD(P)H NAD P H oxidase (NOX-2, NOX-2 p22 and p40 was higher in diabetic mice than in control
7662	NCF4	neutrophil cytosolic factor 4, 40kDa	p40	0.3	for NAD(P)H NAD P H oxidase (NOX-2, NOX-2 p22 and p40 were identical to the mRNA expression in isolated coronary arterioles
2578	CYBB	cytochrome b-245, beta polypeptide (chronic granulomatous disease)	NOX-2	0.0	of protein expression for NAD(P)H NAD P H oxidase (NOX-2, NOX-2 p22 and p40 were identical to the mRNA expression in
2577	CYBA	cytochrome b-245, alpha polypeptide	p22	0.0	protein expression for NAD(P)H NAD P H oxidase (NOX-2, NOX-2 p22 and p40 were identical to the mRNA expression in isolated
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	We believe that TNF-alpha is further upstream in the hierarchy because TNF-alpha induces endothelial
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	believe that TNF-alpha is further upstream in the hierarchy because TNF-alpha induces endothelial dysfunction in the prediabetic metabolic syndrome_amp_#8212 presumably before
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	results provide support for our idea that the interaction between TNF-alpha and RAGE contributes perhaps even by amplifying one another toward
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-alpha	2.7	into a novel therapeutic target for cardiovascular diseases associated with TNF-alpha and AGE/RAGE AGE RAGE signaling
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	tion endothelial dysfunction in type 2 diabetes results in part from elevated production of superoxide o 2 induced by the interaction of advanced glycation end products age /receptor for age rage and tnf alpha signaling.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	we assessed the role of age/rage and tnf alpha signaling in endothelial dysfunction in type 2 diabetic lepr mice by evaluation of endothelial function in isolated coronary resistance vessels of normal control nondiabetic m lepr and diabetic mice.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	we also observed in diabetic mice that augmented rage signaling augmented expression of tnf alpha because this increase was attenuated by srage or nf kappab inhibitor mg132.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	these results indicate that age/rage signaling plays a pivotal role in regulating the production/expression of tnf alpha oxidative stress and endothelial dysfunction in type 2 diabetes.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tumor necrosis factor alpha	1.0	we reported previously 10 19 29 that the inflammatory cytokine tumor necrosis factor alpha tnf alpha plays a pivotal role in endothelial dysfunction; the neutralizing antibody to tnf alpha restored blunted dilation in diabetic rats 19 and diabetic mice null for tnf alpha did not show endot
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	we reported previously 10 19 29 that the inflammatory cytokine tumor necrosis factor alpha tnf alpha plays a pivotal role in endothelial dysfunction; the neutralizing antibody to tnf alpha restored blunted dilation in diabetic rats 19 and diabetic mice null for tnf alpha did not show endothelial dysfunction 10 .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	restored blunted dilation in diabetic rats 19 and diabetic mice null for tnf alpha did not show endothelial dysfunction 10 .
6081	INS	insulin	insulin	1.0	tnf alpha also affects intracellular insulin signaling in fat skeletal muscle and other insulin sensitive tissues by inhibiting kinase activity in the proximal part of the insulin signaling pathway 20 .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	tnf alpha also affects intracellular insulin signaling in fat skeletal muscle and other insulin sensitive tissues by inhibiting kinase activity in the proximal part of the insulin signaling pathway 20 .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	we found that tnf alpha contributes to oxidative stress in diabetes which may explain in part elevations in oxidative stress in diabetes.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	however there are other possible contributors to the increased oxidative stress in diabetes which could serve to amplify the effects of tnf alpha.
6081	INS	insulin	insulin	1.0	recent evidence suggests that inflammation plays a role in the development of insulin resistance and is a predictor of the development of type 2 diabetes mellitus 2 .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	therefore we proposed that age/rage contributes to endothelial dysfunction both directly and by regulating the production and expression of tnf alpha in type 2 diabetes.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	the latter proposition is based on observations showing that nuclear factor kappab nf kappab a transcription factor activated by inflammation and oxidative stress plays a key role in tnf alpha expression.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	accordingly we evaluated the expression of age/rage and tnf alpha in coronary arterioles in type 2 diabetic and normal control nondiabetic mice and determined whether age/rage signaling would compromise endothelial dilation and produce reactive oxygen species ros .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	we also tested whether age/rage signaling leads to tnf alpha expression and production in diabetes.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	heterozygote controls m lepr wild type wt controls homozygote type 2 diabetes lepr diabetic and lepr null for tnf alpha db /db mice were purchased from jackson laboratory and maintained on a normal rodent chow diet.
6554	LEPR	leptin receptor	leptin receptor	1.0	the db /db mice show the phenotype of hyperglycemia and obesity the diabetic phenotype that is consistent with the penetrance of the leptin receptor mutation.
6081	INS	insulin	insulin	1.0	plasma insulin levels were analyzed with a radioimmunoassay kit linco st charles mo .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	treatment with tnf alpha neutralization soluble rage and mg132.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	the neutralizing antibody to tnf alpha anti tnf 10 was 2e2 monoclonal antibody 2e2 mab 94021402; national cancer institute biological resources branch .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	at 12 16 wk of age all mice received the neutralizing anti tnf 2e2 mab 0.625 mg_amp_#183;ml _amp_#183;kg _amp_#183;day ip 3 days ; dosage was based on our estimates of tnf alpha expression in the low nanogram or picogram range and this dosage is 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 and this dosage is 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	tagonize rage signaling we administered srage a gift from a m schmidt; 80 microg_amp_#183;mouse _amp_#183;day ip to control and diabetic mice for 10 days to determine the interaction between rage and tnf alpha in type 2 diabetes and to determine whether rage affects coronary arterial dilations mediated by no.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	protein expression of rage tnf alpha and nf kappab by western blot analyses.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	rage tnf alpha and nf kappab protein expression were detected by western blot analysis with the use of tnf alpha primary antibodies santa cruz or rage or nf kappab primary antibody abcam in control mice diabetic mice diabetic mice treated with anti tnf 0.625 mg_amp_#183;ml _amp_#183;kg _amp_#183;day ip 3 days d
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	our findings support the concept that age/rage and tnf alpha signaling is key to the production of ros; then age/rage and tnf alpha signaling interact to amplify the oxidative stress and induce endothelial dysfunction in diabetic mice.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	role of tnf alpha and age/rage signaling in type 2 diabetes.
12663	VCAM1	vascular cell adhesion molecule 1	vascular cell adhesion molecule 1	1.0	activation of rage by its various ligands reportedly induces a variety of proinflammatory and procoagulant cellular responses resulting from the activation of nf kappab including the expression of vascular cell adhesion molecule 1 vcam 1 tnf alpha il 6 and tissue factor tf 24 .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	nds reportedly induces a variety of proinflammatory and procoagulant cellular responses resulting from the activation of nf kappab including the expression of vascular cell adhesion molecule 1 vcam 1 tnf alpha il 6 and tissue factor tf 24 .
6018	IL6	interleukin 6 (interferon, beta 2)	il 6	1.0	edly induces a variety of proinflammatory and procoagulant cellular responses resulting from the activation of nf kappab including the expression of vascular cell adhesion molecule 1 vcam 1 tnf alpha il 6 and tissue factor tf 24 .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	nf kappab will induce expression of tnf alpha 5 23 .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	accordingly we determined whether age/rage signaling leads to tnf alpha expression and production in diabetes.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	our results showed that protein expression of rage tnf alpha and nf kappab was elevated in type 2 diabetes.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	in type 2 diabetic mice neutralizing antibody to tnf alpha the free radical scavenger tempol srage to corrupt age/rage signaling or the nf kappab inhibitor mg132 decreased the protein expression of rage but srage and mg132 also attenuated tnf alpha expressio
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	the free radical scavenger tempol srage to corrupt age/rage signaling or the nf kappab inhibitor mg132 decreased the protein expression of rage but srage and mg132 also attenuated tnf alpha expression.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	these data provided the evidence for the interaction of age/rage with tnf alpha which may then stimulate the production of o 2 via nf kappab in type 2 diabetes.
4983	HMGB1	high-mobility group box 1	amphoterin	1.0	the generation of age and augmentation of proinflammatory mechanisms in the vessel at least in part via accumulation of s100/calgranulins and amphoterin released from activated inflammatory cells provides a potent feedback loop for sustained oxidant stress ongoing generation of age and vascular perturbation.
6081	INS	insulin	insulin	1.0	it is provocative to note that despite the similarities in glucose body weight lipid level insulin hba1c the index of age accumulation and bp in diabetic animals endothelial function was better in db /db and in lepr mice treated with anti tnf or srage.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	together our results indicate that the impaired vasodilation may result from increased expression/production of tnf alpha and age/rage signaling in type 2 diabetes.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	tnf alpha produces a rapid inhibitory action on no in the endothelium via activation of a sphingomyelinase/ceramide signaling pathway; this mechanism purportedly mediates the action of tnf alpha thereby contributing to vascular endothelial dysfunction in coronary circulation under different pathological conditions with increased cytokines 12 15 29 .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	we found elevations of tnf alpha expression in diabetic mice; srage decreased tnf alpha expression in diabetic mice but did not affect tnf alpha expression in control mice.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	the exact reason why tnf alpha is elevated_amp_#8212;obesity diabetes hyperlipidemia or some or all of these conditions_amp_#8212;is critical.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	we examined the role of age/rage signaling in the expression of tnf alpha to better understand signaling mechanisms responsible for tnf alpha expression.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	our findings indicate that age/rage signaling plays a pivotal role in regulation of tnf alpha expression.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	furthermore srage decreased tnf alpha protein expression in diabetic mice 10 .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	our results support the concept that the interaction of tnf alpha with age/rage contributes to endothelial dysfunction in diabetic mice.
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	nitric oxide synthase	1.0	age also may decrease no availability by decreasing nitric oxide synthase nos activity 4 .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	in our previous study 10 we confirmed the links among tnf alpha nad p h oxidase ros and impaired vasodilation in coronary arterioles in type 2 diabetes.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	this study provides further experimental evidence for an interactive signaling pathway of age/rage and tnf alpha.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	age/rage appear to sum with tnf alpha to induce the endothelial dysfunction in type 2 diabetes.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	because tnf alpha has four nf kappab sites in its promoter we postulate that age/rage signaling increases tnf alpha expression.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	key to the production of ros is age/rage and tnf alpha signaling.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	we have shown interactions among oxidative stress age/rage and tnf alpha because oxidative stress induces nf kappab and this transcription factor induced both rage and tnf alpha expression and tnf alpha induced rage expression fig 7 .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	western blot analysis for tnf alpha protein expression a and b and nf kappab protein expression c .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	schematic figure showing the interactions among tnf alpha age/rage and nf kappab signaling.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	key to the production of ros is age/rage and tnf alpha signaling.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	we have shown interactions among oxidative stress age/rage and tnf alpha because oxidative stress induces nf kappab this transcription factor can induce both rage and tnf alpha expression and tnf alpha can induce rage expression.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	ec endothelial cells; vsmcs vascular smooth muscle cells; tnfr tnf alpha receptor.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	protein expression of tnf alpha and nf kappab in isolated coronary arterioles.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	tnf alpha expression fig 5 a and b was elevated over twofold and nf kappab expression fig 5 c was elevated about fourfold in diabetic mice. srage or mg132 decreased tnf alpha and nf kappab expression in diabetic mice but did not affect expression in control mice.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	we believe that tnf alpha is further upstream in the hierarchy because tnf alpha induces endothelial dysfunction in the prediabetic metabolic syndrome_amp_#8212;presumably before age/rage signaling is pivotal.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tnf alpha	1.0	together these results provide support for our idea that the interaction between tnf alpha and rage contributes perhaps even by amplifying one another toward the evolution of endothelial dysfunction and vascular disease in diabetes.
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 tnf alpha and age/rage signaling.