Dehydroepiandrosterone inhibits the TNF-alpha-induced inflammatory response in human umbilical vein endothelial cells

Gutiérrez, Gisela; Mendoza, Criselda; Zapata, Estrella; Montiel, Angélica; Reyes, Elba; Montaño, Luis F.; López‐Marure, Rebeca

doi:10.1016/j.atherosclerosis.2006.02.031

Cited by 56 publications

(43 citation statements)

References 30 publications

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“…Thus, NADPH oxidase plays a crucial role in high glucose-stimulated production of superoxide in human endothelial cells. As previously described, ROS plays a pivotal role in mediating the response of the endothelium to high glucose and the augmented intracellular ROS production can regulate redox-sensitive genes such as adhesion molecules (Gutiérrez et al, 2007). The above observation showed that RXR ligands and NADPH oxidase inhibitors exerted similar inhibitory effects on high glucose-induced inflammation and NF-κB activation, suggesting that RXR agonists might interfere with NADPH oxidase activation.…”

Section: Rxr Agonists Reduce High Glucose-induced Activation Of Nadphsupporting

confidence: 74%

RXR agonists inhibit high glucose-induced upregulation of inflammation by suppressing activation of the NADPH oxidase-nuclear factor-κB pathway in human endothelial cells

Ning¹,

Zhu²,

Chai³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. An inflammatory response induced by high glucose is a cause of endothelial dysfunction in diabetes and is an important contributing link to atherosclerosis. Diabetes is an independent risk factor of atherosclerosis and activation of retinoid X receptor (RXR) has been shown to exert anti-atherogenic effects. In the present study, we examined the effects of the RXR ligands 9-cis-retinoic acid (9-cis-RA) and SR11237 on high glucose-induced inflammation in human umbilical endothelial vein endothelial cells (HUVECs) and explored the potential mechanism. RXR agonists inhibit inflammation through NADPH-NFκBOur results showed that the inflammation induced by high-glucose in HUVECs was mainly mediated by the activation of nuclear factor-B (NF-κB). High glucose-induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were in comparison, significantly decreased by treatment with RXR. The effect of RXR agonists was mainly due to the inhibition of NF-κB activation. Using pharmacological inhibitors and siRNA, we confirmed that nicotinamide adenine dinucleotide phosphate (NADPH) oxidase was an upstream activator of NF-κB. Furthermore, RXR agonists significantly inhibited high glucose-induced activation of NADPH oxidase and significantly decreased the production of reactive oxygen species (ROS). To explore whether the rapid inhibitory effects of RXR agonists were in fact mediated by RXR, we examined the effect of RXR downregulation by RXR siRNA. Our results showed that RXR siRNA largely abrogated the effects of RXR agonists, suggesting the requirement of RXR expression. Therefore, we have shown that RXR is involved in the regulation of NADPH oxidase-NF-κB signal pathway, as the RXR ligands antagonized the inflammatory response in HUVECs induced by high glucose.

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Section: Rxr Agonists Reduce High Glucose-induced Activation Of Nadphsupporting

confidence: 74%

RXR agonists inhibit high glucose-induced upregulation of inflammation by suppressing activation of the NADPH oxidase-nuclear factor-κB pathway in human endothelial cells

Ning¹,

Zhu²,

Chai³

et al. 2013

Genet. Mol. Res.

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“…Dehydroepiandrosterone delays LDL oxidation in vitro and attenuates several oxLDL-induced inflammatory responses in endothelial cells, such as ICAM-1, PECAM-1 and VCAM-1; DHEA inhibited ox-LDL-induced ROS production; and DHEA increased AP-1 translocation [24] . Dehydroepiandrosterone inhibits the tumor necrosis factor-α-induced inflammatory response in human umbilical vein endothelial cells [41] . Therefore, its potential anti-inflammatory properties should be evaluated for the treatment of chronic inflammatory diseases such as atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Dehydroepiandrosterone anti-atherogenesis effect is not via its conversion to estrogen

Cheng

Ruan

2008

Acta Pharmacol Sin

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Aim: This study was conducted to demonstrate the anti-atherosclerotic effect of dehydroepiandrosterone (DHEA) and to investigate its possible mechanisms and whether this effect is related to its conversion to estrogen. Methods: Forty male New Zealand White rabbits aged 3 months were divided into 5 groups (n=8 per group) and fed different diets for 10 weeks. Serum lipid levels, the area of atherosclerotic lesions and the mRNA levels of monocyte chemoattractant protein-1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1) in aortic lesions were measured. Then cultured vascular smooth muscle cells (VSMCs) stimulated by oxidized low density lipoprotein-cholesterol (ox-LDL) were treated by DHEA. The gene and protein expression levels of MCP-1 and VCAM-1 in VSMCs was detected. The plasmid with or without the gene of cytochrome P450 aromatase (CYP19) was transient transfected into cultured VSMCs respectively. Twenty hours later, the cells were stimulated with ox-LDL and DHEA. Results: DHEA could obviously decrease the area of atherosclerotic lesions and the expressions of MCP-1 and VCAM-1 in aortic lesions. But all-trans retinoic acid (atRA) which was reported would limit restenosis after balloon angioplasty had no visible synergistic effect with DHEA. DHEA could also reduce ox-LDL-induced MCP-1 and VCAM-1 expression in untransfected or transfected VSMCs. Conclusion:The anti-atherosclerotic effect of DHEA had nothing to do with the catalysis of cytochrome P450 aromatase (CYP19), or was not related to its conversion to estrogen.

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“…In vitro release in the haase environment In vitro iMΦ-targeting property 35,36 Finally, the expression of CD44 receptors on HUVEC monolayer and the permeability of HUVEC monolayer after stimulation with TNF-α and ox-LDL for 12 h were analyzed to validate the formation of the injured HUVECs/iMΦ co-culture system.…”

Section: Morphologymentioning

confidence: 99%

Plaque-hyaluronidase-responsive high-density-lipoprotein-mimetic nanoparticles for multistage intimal-macrophage-targeted drug delivery and enhanced anti-atherosclerotic therapy

Zhang¹,

He²,

Jiang³

et al. 2017

IJN

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Dehydroepiandrosterone inhibits the TNF-alpha-induced inflammatory response in human umbilical vein endothelial cells

Cited by 56 publications

References 30 publications

RXR agonists inhibit high glucose-induced upregulation of inflammation by suppressing activation of the NADPH oxidase-nuclear factor-κB pathway in human endothelial cells

RXR agonists inhibit high glucose-induced upregulation of inflammation by suppressing activation of the NADPH oxidase-nuclear factor-κB pathway in human endothelial cells

Dehydroepiandrosterone anti-atherogenesis effect is not via its conversion to estrogen

Plaque-hyaluronidase-responsive high-density-lipoprotein-mimetic nanoparticles for multistage intimal-macrophage-targeted drug delivery and enhanced anti-atherosclerotic therapy

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