Oxidized-LDL induce apoptosis in HUVEC but not in the endothelial cell line EA.hy 926

Claise, Catherine; Edeas, Marvin; Chaouchi, Nadia; Chalas, Jacqueline; Capel, Liliane; Kalimouttou, Sendil; Vázquez, Aimé; Lindenbaum, A

doi:10.1016/s0021-9150(99)00170-7

Cited by 45 publications

(35 citation statements)

References 54 publications

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“…HUVECs were much more susceptible to H 2 O 2 -induced cell injury than the EAhy926 cells, as reported by other groups. 36 HUVECs grown on gelatin-coated wells and exposed to 4mM H 2 O 2 for 40 minutes resulted in a decrease in cell viability from 100% plus or minus 14.5% to 59.7% plus or minus 22.0% (n ϭ 5; Figure 6C). This reduction in cell viability was completely abrogated by preincubating cells with n␤2GPI pretreated with TRX-R/NADPH-activated TRX-1, increasing cell viability to the level of that seen with cells incubated with media alone (n ϭ 3; P Ͻ .001; Figure 6D (n ϭ 3).…”

Section: One or More Free Thiols Generated Within ␤2gpi By Activated mentioning

confidence: 99%

Naturally occurring free thiols within β2-glycoprotein I in vivo: nitrosylation, redox modification by endothelial cells, and regulation of oxidative stress–induced cell injury

Ioannou

Zhang

Passam

et al. 2010

Blood

109

113

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␤2-Glycoprotein I (␤2GPI) is an evolutionary conserved, abundant circulating protein. Although its function remains uncertain, accumulated evidence points toward interactions with endothelial cells and components of the coagulation system, suggesting a regulatory role in vascular biology. Our group has shown that thioredoxin 1 (TRX-1) generates free thiols in ␤2GPI, a process that may have a regulatory role in platelet adhesion. This report extends these studies and shows for the first time evidence of ␤2GPI with free thiols in vivo in both multiple human and murine serum samples. To explore how the vascular surface may modulate the redox status of ␤2GPI, unstimulated human endothelial cells and EAhy926 cells are shown to be capable of amplifying the effect of free thiol generation within ␤2GPI. Multiple oxidoreductase enzymes, such as endoplasmic reticulum protein 46 (ERp 46) and TRX-1 reductase, in addition to protein disulfide isomerase are secreted on the surface of endothelial cells. Furthermore, one or more of these generated free thiols within ␤2GPI are also shown to be nitrosylated. Finally, the functional significance of these findings is explored, by showing that free thiol-containing ␤2GPI has a powerful effect in protecting endothelial cells and EAhy926 cells from oxidative stress-induced cell death. IntroductionThioredoxin 1 (TRX-1) is a ubiquitous, 12-kDa oxidoreductase enzyme whose multiple intracellular functions include reducing protein disulfides, scavenging oxygen free radicals, and redox regulation of signaling pathways involved in cell growth, apoptosis, and inflammation. 1 TRX-1 requires nitrosylation of the unpaired cysteine (Cys69) thiol to mediate key intracellular functions. 2 S-nitrosylation of thiols has been implicated as being important in several multisystemic physiologic and pathologic processes pertaining to hemostasis and vascular disease. 3 In addition to being a key intracellular molecule, TRX-1 is an enzyme also found in circulating plasma. It is released from cells in response to oxidative stress 4,5 and is found at higher levels in the circulation in a variety of acute and chronic inflammatory or metabolic conditions associated with an increase in systemic oxidative stress load. [6][7][8] Studies have shown that exogenous administration of TRX-1 exerts a protective role in animal models of high oxidative stress such as smoking and rheumatoid arthritis, 9,10 both of which represent risk factors for cardiovascular morbidity in humans. 11 Oxidative stress is known to be associated with vascular pathology in terms of promoting atherosclerotic plaque development, rupture and atherothrombosis. 12 However, the extracellular mechanism through which elevated TRX-1 may mediate a protective effect against oxidative stress-induced vascular injury has not been fully delineated.␤ 2 -Glycoprotein I (␤2GPI) is an evolutionary conserved 50-kDa plasma protein. The function of ␤2GPI remains uncertain, although it is thought to play a role in apoptotic cell clearance and coagulation through m...

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Section: One or More Free Thiols Generated Within ␤2gpi By Activated mentioning

confidence: 99%

Naturally occurring free thiols within β2-glycoprotein I in vivo: nitrosylation, redox modification by endothelial cells, and regulation of oxidative stress–induced cell injury

Ioannou

Zhang

Passam

et al. 2010

Blood

109

113

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“…The human EA.Hy926 endothelial cell line, generated from fusion of the epithelial A549 cell line with human umbilical vein endothelial cell (HUVEC) [29][30][31], was bought from the cell bank in Key Laboratory of Transplant Engineering and Immunology of Ministry of Health, West China Hospital Sichuan University. Cells were kept in liquid nitrogen tank until use.…”

Section: Cell Culturementioning

confidence: 99%

Galvanotactic Migration of EA.Hy926 Endothelial Cells in a Novel Designed Electric Field Bioreactor

Long

Yang

Wang

2011

Cell Biochem Biophys

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Endogenous direct current electric fields (dcEFs) play a significant role in major biological processes such as embryogenesis, wound healing, and tissue regeneration. In this study, the galvanotaxis of human umbilical vein endothelial cell line EA.Hy926 was investigated by using a novel designed bioreactor. The physical features of the bioreactor were discussed and analyzed by both numerical simulation method and equivalent circuit model method. EA.Hy926 cells were cultured in the bioreactor for 10-24 h under 50-250 mV/mm dcEFs. Cell migration direction, distance, and velocity were recorded under an online time-lapse microscope. The effects of serum and growth factor on cell galvanotatic migration were investigated. To further explore the role of dcEFs in regulating endothelial cells, we analyzed the endothelial cell proliferation and secretion of nitric oxide (NO), endothelin-1 (ET-1) in response to dcEFs of physiological strength. Our results showed that EA.Hy926 cells had an obvious directional migration to the cathode, and the EF-directed migration was voltage dependent. The results also showed dcEFs did not affect cell proliferation, but affected the productions of NO and ET-1. Our study also showed the novel bioreactor, with a compact and planar style, makes it more convenient and more reasonable for EF stimulation experiments than earlier chamber designs.

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“…3,4 Tissue culture experiments have indicated that oxLDL exposure leads to extensive apoptosis in vascular smooth muscle cells, 5 human coronary cells, 6 and human umbilical venous endothelial cells (HUVECs). 7,8 It has been further shown that the p38 mitogen-activated protein kinase (MAPK) is a downstream effector of the oxLDLinduced apoptotic process. 5 Little is known, however, about the upstream molecular mechanisms that regulate this process.…”

mentioning

confidence: 99%

Protection Against Oxidized Low-Density Lipoprotein–Induced Vascular Endothelial Cell Death by Integrin-Linked Kinase

Zhang

Hu²,

Li³

2001

Circulation

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Background-Integrin-linked kinase (ILK) is a protein that plays important roles in extracellular matrix-mediated signaling. It has been shown that ILK is expressed preferentially in cardiac and skeletal muscles. Evidence points to its role as an upstream regulator of protein kinase B, a critical player in apoptosis. Because oxidized LDL (oxLDL) is thought to promote atherogenesis by causing the apoptosis of endothelial cells, we investigated the potential roles that ILK may play in oxLDL-induced apoptosis in vascular endothelial cells. Methods and Results-Transcriptional and translational levels of ILK were investigated with reverse-transcriptase polymerase chain reaction and Western analysis. oxLDL treatment induced both the transcription and the translation of the ILK gene in endothelial cells. A recombinant adenovirus vector encoding the ILK gene was constructed to investigate its potential role in oxLDL-induced apoptosis in human umbilical vein endothelial cells and mouse lymphoid vein endothelial cells transformed by simian virus 40. In both types of cells, overexpression of the ILK gene significantly prevented oxLDL-induced apoptosis or cell death, as evaluated by 2 independent assay methods. Furthermore, we showed that ILK could inhibit oxLDL-induced upregulation of the kinase activity of p38 mitogen-activated protein kinase, which is often associated with stress-induced pro-apoptotic signal transduction. Finally, examination of other factors, such as bcl-2, bcl-xl, caspase 3, and caspase 9, demonstrated significant changes that were correlated with oxLDL treatment and ILK overexpression. Key Words: oxygen Ⅲ lipoproteins Ⅲ endothelium Ⅲ apoptosis Ⅲ kinases O xidized LDL (oxLDL) has been implicated in atherosclerosis in both epidemiological and laboratory studies. 1,2 The precise role that oxLDL plays in atherogenesis is unknown. There is, however, increasing evidence to suggest that oxLDL-induced injury of the vascular wall is critical because it may be the initiating event that leads to the inflammatory responses now recognized to be the main cause of atherosclerosis. How does oxLDL induce injury to the vascular wall? Many recent studies suggest that oxLDLinduced apoptosis in the vascular smooth muscle cells or vascular endothelial cells may be the key. In support of this theory, several studies have demonstrated the presence of apoptosis in human and experimental atherosclerotic plaques. 3,4 Tissue culture experiments have indicated that oxLDL exposure leads to extensive apoptosis in vascular smooth muscle cells, 5 human coronary cells, 6 and human umbilical venous endothelial cells (HUVECs). 7,8 It has been further shown that the p38 mitogen-activated protein kinase (MAPK) is a downstream effector of the oxLDLinduced apoptotic process. 5 Little is known, however, about the upstream molecular mechanisms that regulate this process. Conclusion-ILKIn our efforts to identify novel signal-transduction pathways further upstream, we came across integrin-linked kinase (ILK) by virtue of its upregulation in oxLD...

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Oxidized-LDL induce apoptosis in HUVEC but not in the endothelial cell line EA.hy 926

Cited by 45 publications

References 54 publications

Naturally occurring free thiols within β2-glycoprotein I in vivo: nitrosylation, redox modification by endothelial cells, and regulation of oxidative stress–induced cell injury

Naturally occurring free thiols within β2-glycoprotein I in vivo: nitrosylation, redox modification by endothelial cells, and regulation of oxidative stress–induced cell injury

Galvanotactic Migration of EA.Hy926 Endothelial Cells in a Novel Designed Electric Field Bioreactor

Protection Against Oxidized Low-Density Lipoprotein–Induced Vascular Endothelial Cell Death by Integrin-Linked Kinase

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