The inhibitory effect of simvastatin on the ADMA-induced inflammatory reaction is mediated by MAPK pathways in endothelial cells

Jiang, Jun-Lin; Wang, Shan WangS.; Li, Nian-Sheng LiN.S.; Zhang, Xiao-Hong ZhangX.H.; Deng, Han-Wu; Li, Yuan-Jian LiY.J.

doi:10.1139/o06-146

Cited by 47 publications

(29 citation statements)

References 38 publications

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“…In accordance with the previous observations [25], treatment with ox-LDL (100 lg/ml) for 24 h significantly increased the expression of ICAM-1 and P-selectin in endothelial cells. Pretreatment of cells with delphinidin (50, 100, or 200 lM) concentration-dependently reduced the expression of ICAM-1 and P-selectin in endothelial cells (both Western blotting and ELISA; Fig.…”

Section: Effect Of Delphinidin On the Expression Of Adhesion Moleculesupporting

confidence: 92%

Inhibitory Effect of Delphinidin on Monocyte–Endothelial Cell Adhesion Induced by Oxidized Low-Density Lipoprotein via ROS/p38MAPK/NF-κB Pathway

Chen

Jin

et al. 2011

Cell Biochem Biophys

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Monocyte adhesion to the vascular endothelium and their subsequent trans-endothelial migration are pivotal early events in atherogenesis. In this study, the effect of delphinidin, belonging to the group of anthocyanin, on adhesion of monocytes to endothelial cells induced by ox-LDL was investigated. The results showed that the pre-treatment with delphinidin (50, 100, or 200 μM) dose-dependently decreased the ox-LDL-induced up-regulation of the expression of ICAM-1 and P-selectin, and the enhanced adhesion and transmigration of monocytes. To determine the role of ROS/p38MAPK/NF-κB pathway, intracellular ROS level, p38MAPK protein expression, NF-κB transcription activity and protein expression, IκB-α degradation, NADPH oxidase subunit (Nox2 and p22phox) protein, and mRNA expression were measured. The results showed that delphinidin attenuated ox-LDL-induced generation of ROS, p38MAPK protein expression, NF-κB transcription activity and protein expression, IκB-α degradation, NADPH oxidase subunit (Nox2 and p22phox) protein and mRNA expression in endothelial cells in a dose-dependent manner. These results suggest that delphinidin attenuates ox-LDL induced expression of adhesion molecules (P-selectin and ICAM-1) and the adhesion of monocytes to endothelial cells by inhibiting ROS/p38MAPK/NF-κB pathway. These findings provide a basis for the design of potent antiatherosclerotic agents that will have therapeutic potential in the prevention of AS.

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Section: Effect Of Delphinidin On the Expression Of Adhesion Moleculesupporting

confidence: 92%

Inhibitory Effect of Delphinidin on Monocyte–Endothelial Cell Adhesion Induced by Oxidized Low-Density Lipoprotein via ROS/p38MAPK/NF-κB Pathway

Chen

Jin

et al. 2011

Cell Biochem Biophys

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“…There are few hypotheses on how statins influence ADMA levels. One of them concerns the inhibition of ADMA-induced inflammatory reaction, modulated by mitogen-activated protein kinase (MAPK) pathway in human endothelial cells 44 . Statins also activate the transcription factor sterol response element binding protein (SREBP) through decreasing content of the cholesterol in the membrane 45 .…”

Section: Discussionmentioning

confidence: 99%

A systematic review and meta-analysis on the effect of statins on plasma asymmetric dimethylarginine concentrations

et al. 2015

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“…The NF-kB signaling pathway may be involved in the inflammatory reaction induced by ADMA [20]. Our recent results showed that ADMA promoted nuclear DNA binding to NF-kB in HUVECs, while actin-targeting drugs interfered with nuclear NF-kB DNA-binding activity, thereby inhibiting expression of ICAM-1 [10].…”

Section: Discussionmentioning

confidence: 99%

Disruption of asymmetric dimethylarginine-induced RelA/P65 association with actin in endothelial cells

Wei

Zhang

Wang

et al. 2013

ABBS

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Asymmetric dimethylarginine (ADMA) activates nuclear factor (NF)-kB in endothelial cells, while actin-stabilizing or -destabilizing drugs prevent ADMA-induced activation of NF-kB. Here we investigated how actin-targeting drugs regulated ADMA-induced NF-kB activation in endothelial cells. Human umbilical vein endothelial cells were treated with ADMA for 24 h in the absence and presence of cytochalasin D or jasplakinolide. Expression levels of proteins and genes were measured by immunoblotting and reversetranscription polymerase chain reaction, respectively. Chromatin immunoprecipitation was used to detect the binding of NF-kB to the vascular cell adhesion molecule 1 (VCAM-1) promoter. The association of actin with RelA/ P65 was detected by immunoprecipitation. It was demonstrated that ADMA induced IkBa degradation, increased nuclear RelA/P65 translocation, and promoted the binding of NF-kB to the VCAM-1 promoter. Consequently, this increased the expression of VCAM-1. In parallel studies, actin-stabilizing and -destabilizing drugs decreased ADMAinduced RelA/P65 nuclear translocation, interfered with NF-kB binding to the VCAM-1 promoter and prevented the expression of VCAM-1. This was independent of total RelA/ P65 levels and ADMA-induced IkBa degradation. Most importantly, the association of RelA/P65 with actin was increased after stimulation with ADMA, and impaired after treatment with actin-targeting drugs. In brief, actinstabilizing or -destabilizing drugs interfere with the ADMAinduced association of RelA/P65 with actin, and consequently disrupt NF-kB activation.

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The inhibitory effect of simvastatin on the ADMA-induced inflammatory reaction is mediated by MAPK pathways in endothelial cells

Cited by 47 publications

References 38 publications

Inhibitory Effect of Delphinidin on Monocyte–Endothelial Cell Adhesion Induced by Oxidized Low-Density Lipoprotein via ROS/p38MAPK/NF-κB Pathway

Inhibitory Effect of Delphinidin on Monocyte–Endothelial Cell Adhesion Induced by Oxidized Low-Density Lipoprotein via ROS/p38MAPK/NF-κB Pathway

A systematic review and meta-analysis on the effect of statins on plasma asymmetric dimethylarginine concentrations

Disruption of asymmetric dimethylarginine-induced RelA/P65 association with actin in endothelial cells

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