Role of Caveolin-1 in Egcg-Mediated Protection Against Linoleic Acid-Induced Endothelial Cell Activation

Hennig, Bernhard; Zheng, Yangfan; Smart, Elizabeth; Toborek, Michał

doi:10.1016/s1567-5688(08)70264-2

Cited by 4 publications

(8 citation statements)

References 22 publications

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“…With regard to the underlying mechanisms of antiinflammation, EGCG inhibits angiotensin II-induced adhesion molecule expression (4) and acts as a potent inhibitor of NF-B, a key transcription factor in the expression of inflammatory cytokines (41). In addition, recent studies have shown that EGCG improves endothelium-dependent vasodilation (23) and downregulates endothelial inflammatory parameters by modulating caveolae-regulated cell signaling (59). Together, these findings suggest that EGCG might play a role in the prevention of cardiovascular diseases.…”

Section: Discussionmentioning

confidence: 99%

EGCG protects against oxidized LDL-induced endothelial dysfunction by inhibiting LOX-1-mediated signaling

Song

Yeh

et al. 2010

Journal of Applied Physiology

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Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), originally identified as the major receptor for oxidized low-density lipoprotein (oxLDL) in endothelial cells, plays a major role in the pathology of vascular diseases. Green tea consumption is associated with reduced cardiovascular mortality in some epidemiological studies. In the present study, we hypothesized that the most abundant polyphenolic compound in tea, epigallocatechin-3-gallate (EGCG), can downregulate parameters of endothelial dysfunction by modulating LOX-1-regulated cell signaling. In cultured human umbilical vein endothelial cells (HUVECs), exposure to oxLDL (130 microg/ml), which led to an increase in LOX-1 expression at the RNA and protein levels, was abrogated by addition of EGCG or DPI, a well-known inhibitor of flavoproteins, suggesting the involvement of NADPH oxidase. Furthermore, oxLDL rapidly activated the membrane translocation of Rac-1 and p47phox and the subsequent induction of ROS generation, which was suppressed markedly by pretreatment with EGCG or anti-LOX-1 monoclonal antibody. OxLDL also increased p38 MAPK phosphorylation and decreased phosphorylation of the amino-terminal region of Akt, with maximal induction at about 30 min, and NF-kappaB phosphorylation within 1 h, resulting in redox-sensitive signaling. In addition, oxLDL diminished the expression of endothelial nitric oxide synthase (eNOS), enhanced the expression of endothelin-1 and adhesion molecules (ICAM, E-selectin, and monocyte chemoattractant protein-1), and increased the adherence of monocytic THP-1 cells to HUVECs. Pretreatment with EGCG, however, exerted significant cytoprotective effects in all events. These data suggest that EGCG inhibits the oxLDL-induced LOX-1-mediated signaling pathway, at least in part, by inhibiting NADPH oxidase and consequent ROS-enhanced LOX-1 expression, which contributes to further ROS generation and the subsequent activation of NF-kappaB via the p38 MAPK pathway. Results from this study may provide insight into a possible molecular mechanism by which EGCG suppresses oxLDL-mediated vascular endothelial dysfunction.

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Section: Discussionmentioning

confidence: 99%

EGCG protects against oxidized LDL-induced endothelial dysfunction by inhibiting LOX-1-mediated signaling

Song

Yeh

et al. 2010

Journal of Applied Physiology

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“…As LA and oxidative stress were shown to activate the p38 MAPK and Akt signaling pathways , next, we evaluated the possible role of p38 MAPK or Akt in SO‐induced triglyceride accumulation. J774A.1 macrophages were treated with SO in the absence or presence of the p38 MAPK inhibitor SB202190 or the Akt inhibitor LY294002 (10 µM), followed by assessment of cellular triglyceride content.…”

Section: Resultsmentioning

confidence: 99%

“…Under high oxidative stress, the p38 MAPK and Akt signaling pathways are activated in macrophages . These pathways were also demonstrated to be activated by LA exposure to other cells . To elucidate the signaling pathway linking SO or LA‐induced macrophage oxidative stress and triglyceride accumulation, we examined macrophage triglyceride content under SO or LA treatment in the absence or presence of p38 MAPK or Akt inhibitors.…”

Section: Discussionmentioning

confidence: 99%

“…J774A.1 macrophages were treated with increasing concentrations of SO‐based emulsion (up to 500 µg/mL of SO) or with purified LA (up to 250 µg/mL). In some experiments, cells were treated with SO or LA in the absence or presence of NAC (10 mM) , PJ (20 μM gallic acid equivalents, GAE) , the triterpenoid DGAT1 inhibitor OA (75 μM) , p38 MAPK inhibitor SB202190 (10 μM) , or Akt inhibitor LY294004 (10 μM) , with equivalent ethanol/DMSO levels (vehicle control, <0.5%). When using SB202190 or LY294004, cells were pretreated 1 h prior to SO or LA exposure.…”

Section: Methodsmentioning

confidence: 99%

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Supplementation with linoleic acid‐rich soybean oil stimulates macrophage foam cell formation via increased oxidative stress and diacylglycerol acyltransferase1‐mediated triglyceride biosynthesis

et al. 2016

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During the last decades there has been a staggering rise in human consumption of soybean oil (SO) and its major polyunsaturated fatty acid linoleic acid (LA). The role of SO or LA in cardiovascular diseases is highly controversial, and their impact on macrophage foam cell formation, the hallmark of early atherogenesis, is unclear. To investigate the effects of high SO or LA intake on macrophage lipid metabolism and the related mechanisms of action, C57BL/6 mice were orally supplemented with increasing levels of SO-based emulsion or equivalent levels of purified LA for 1 month, followed by analyses of lipid accumulation and peroxidation in aortas, serum and in peritoneal macrophages (MPM) of the mice. Lipid peroxidation and triglyceride mass in aortas from SO or LA supplemented mice were dose-dependently and significantly increased. In MPM from SO or LA supplemented mice, lipid peroxides were significantly increased and a marked accumulation of cellular triglycerides was found in accordance with enhanced triglyceride biosynthesis rate and overexpression of diacylglycerol acyltransferase1 (DGAT1), the key enzyme in triglyceride biosynthesis. In cultured J774A.1 macrophages treated with SO or LA, triglyceride accumulated via increased oxidative stress and a p38 mitogen-activated protein kinase (MAPK)-mediated overexpression of DGAT1. Accordingly, anti-oxidants (pomegranate polyphenols), inhibition of p38 MAPK (by SB202190) or DGAT1 (by oleanolic acid), all significantly attenuated SO or LA-induced macrophage triglyceride accumulation. These findings reveal novel mechanisms by which supplementation with SO or LA stimulate macrophage foam cell formation, suggesting a pro-atherogenic role for overconsumption of SO or LA. © 2016 BioFactors, 43(1):100-116, 2017.

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“…This effect has been largely attributed to the most abundant and most active catechin derivative contained in green tea, (–)‐epigallocatechin gallate (EGCG). Although the precise mechanisms by which EGCG lessens atherogenesis have not been completely defined, much evidence suggests that EGCG may act as a well‐characterized antioxidant with anti‐inflammatory and anti‐proliferative activities [14–16], thereby reducing the risk of atherosclerosis [17,18]. Since few data exist concerning the role of EGCG in the regulation of CRP‐mediated inflammatory process, the inhibitory effect of EGCG on CRP production is worthy of investigation.…”

mentioning

confidence: 99%

(‐)‐Epigallocatechin Gallate Inhibits Endothelin‐1‐Induced C‐Reactive Protein Production in Vascular Smooth Muscle Cells

Wang

Liu

Guo

2010

Basic Clin Pharma Tox

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Abstract:Numerous studies have shown that C-reactive protein (CRP), a pro-inflammation cytokine, makes a direct contribution to atherosclerosis, and that (-)-epigallocatechin gallate (EGCG) is able to exert an anti-atherosclerotic effect by antioxidative and anti-inflammatory activities. Based on our previous study, the effect of EGCG on endothelin-1 (ET-1)-induced CRP production in rat vascular smooth muscle cells (VSMCs) and the possible mechanism were observed. The in vitro experiments showed that EGCG concentration-dependently inhibited ET-1-stimulated expression of CRP both in protein and mRNA levels in VSMCs as determined by the immunocytochemical staining, the enzyme-linked immunosorbent assay and the real-time quantitative polymerase chain reaction (RT-qPCR). The in vivo investigation with the double-labelled immunofluorescence staining and RT-qPCR displayed that EGCG also prevented ET-1-induced CRP expression in protein and mRNA levels in the aortic VSMCs of rats receiving the subchronic infusion of ET-1. In addition, EGCG suppressed reactive oxygen species (ROS) generation evoked by ET-1 in VSMCs as observed by the fluorescence probe. These demonstrate that EGCG may inhibit ET-1-stimulated generation of CRP in VSMCs so to relieve the inflammatory response and oxidative stress via blocking ROS signal, which provides new evidence for an anti-atherosclerotic effect of EGCG.

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Role of Caveolin-1 in Egcg-Mediated Protection Against Linoleic Acid-Induced Endothelial Cell Activation

Cited by 4 publications

References 22 publications

EGCG protects against oxidized LDL-induced endothelial dysfunction by inhibiting LOX-1-mediated signaling

EGCG protects against oxidized LDL-induced endothelial dysfunction by inhibiting LOX-1-mediated signaling

Supplementation with linoleic acid‐rich soybean oil stimulates macrophage foam cell formation via increased oxidative stress and diacylglycerol acyltransferase1‐mediated triglyceride biosynthesis

(‐)‐Epigallocatechin Gallate Inhibits Endothelin‐1‐Induced C‐Reactive Protein Production in Vascular Smooth Muscle Cells

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