Chronic exposure of cultured bovine endothelial cells to oxidized LDL abolishes prostacyclin release.

Thorin, Éric; Hamilton, Carlene A.; Dominiczak, Marek H.; Reid, John L.

doi:10.1161/01.atv.14.3.453

Cited by 49 publications

(20 citation statements)

References 20 publications

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“…3). The inhibition of agonist-stimulated PG!2 generation in our study is consistent with the observations reported by Thorin et al (1994) and may reflect inhibition of the cyclooxygenase pathway and/or receptor activation by histamine. Oxidized LDL and reactive oxygen species influence gene expression and activate nuclear transcription factors (see Andalibi, Liao, Imes, Fogelman & Lusis, 1993;Adcock, Brown, Kwon & Barnes, 1994;Lavrovsky, Schwartzmann, Levere, Kappas & Abraham, 1994;Ares, Kallin, Eriksson & Nilsson, 1995;and see Figs 1 and 3 in Brand, Page, WaIli, Neumeier & Baeuerle, 1997) involved in the expression of iNOS and the antioxidant stress protein haem oxygenase-1 (HO-1), which catalyses metabolism of haem to biliverdin/bilirubin and carbon monoxide (CO; see Maines, Mark & Ewing, 1993).…”

Section: Effects Of Low Density Lipoprotein On Endothelial Cell Prostsupporting

confidence: 93%

“…Prolonged exposure (-3 days) of bovine aortic endothelial cells to oxidized LDL decreases basal and bradykinin-stimulated prostacyclin (PGI2) production (Thorin, Hamilton, Cominiczak & Reid, 1994). However, another study, using the same cell type, reported that native and oxidized glycated LDL increased basal PG!2 production (Kobayashi, Watanabe, Umeda, Taniguchi, Masakado, Yamauchi & Nawata, 1995).…”

Section: Effects Of Low Density Lipoprotein On Endothelial Cell Prostmentioning

confidence: 99%

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Modulation of vascular tone by low density lipoproteins: effects on L‐arginine transport and nitric oxide synthesis

Jay¹,

Chirico²,

Siow³

et al. 1997

Experimental Physiology

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SUMMARYLow density lipoprotein (LDL) plays an important role in atherogenesis. Focal accumulation within the arterial intima of excess amounts of cholesterol-rich LDL leads to the migration and recruitment of monocytes, which then differentiate into macrophages after taking up large amounts of oxidatively modified LDL via their scavenger receptors and become lipid-laden 'foam cells' within the subendothelial space. It is generally accepted that oxidized LDL and hyperlipidaemia impair endothelial-dependent vascular relaxation, yet the existing literature on the effects of oxidatively modified LDL on endothelium-derived nitric oxide (NO) and prostacyclin (PGI2) release is inconclusive, since oxidized LDL has been reported to enhance or reduce NO and PGI2 production. Our studies using cultured human endothelial and smooth muscle cells have established that basal rates of L-arginine (NO precursor) transport, NO and PGI2 production and soluble guanylyl cyclase activity are unaffected by pretreatment (for 1 or 24 h) with native LDL, or with mildly or highly oxidized LDL. In contrast, highly oxidized LDL inhibited histamine-stimulated release of NO and PGI2 from human endothelial cells and induced an adaptive increase in the level of intracellular glutathione in human smooth muscle cells, a response which was prevented by the chain-breaking antioxidant x-tocopherol. Although initial rates of L-arginine transport and basal NO and PGI2 release from human endothelium are unaffected by oxidized LDL, agonist-stimulated release of these vasodilators is markedly attenuated. Elucidation of the mechanisms regulating these responses and their sensitivity to dietary antioxidants could lead to alternative strategies for reducing atherogenesis.

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Section: Effects Of Low Density Lipoprotein On Endothelial Cell Prostsupporting

confidence: 93%

Section: Effects Of Low Density Lipoprotein On Endothelial Cell Prostmentioning

confidence: 99%

Modulation of vascular tone by low density lipoproteins: effects on L‐arginine transport and nitric oxide synthesis

Jay¹,

Chirico²,

Siow³

et al. 1997

Experimental Physiology

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“…Porcine aortic endothelial cells were isolated by enzymatic digestion using type II collagenase as described previously [36]. Cells were grown in Dulbecco's Modified Eagle Medium (DMEM) supplemented with 10% foetal bovine serum, 1% penicillin-streptomycin, and glutamine.…”

Section: Isolation Of Endothelial Cellsmentioning

confidence: 99%

Intracrine endothelin signaling evokes IP3-dependent increases in nucleoplasmic Ca2+ in adult cardiac myocytes

Merlen¹,

Farhat²,

Luo³

et al. 2013

Journal of Molecular and Cellular Cardiology

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Endothelin receptors are present on the nuclear membranes in adult cardiac ventricular myocytes. The objectives of the present study were to determine 1) which endothelin receptor subtype is in cardiac nuclear membranes, 2) if the receptor and ligand traffic from the cell surface to the nucleus, and 3) the effect of increased intracellular ET-1 on nuclear Ca 2+ signalling. Confocal microscopy using fluorescently-labeled endothelin analogs confirmed the presence of ETB at the nuclear membrane of rat cardiomyocytes in skinned-cells and isolated nuclei. Furthermore, in both cardiac myocytes and aortic endothelial cells, endocytosed ET:ETB complexes translocated to lysosomes and not the nuclear envelope. Although ETA and ETB can form heterodimers, the presence or absence of ETA did not alter ETB trafficking. Treatment of isolated nuclei with * Abbreviations: The abbreviations used are: 2-APB, 2-aminoethoxydiphenyl borate; A, Angiotensin II; αAR, α-adrenergic receptor;[Ca 2+ ] n , nucleoplasmic free calcium concentration; CaMKII, Ca 2+ /calmodulin-dependent protein kinase II; DMNB, 4,5-dimethoxynitrobenzyl group; DNA, deoxyribonucleic acid; DCC, 1,3-dicyclohexylcarbodiimide; DCM, dichloromethane; DTT, dithiothreitol; ECE1-a, endothelin converting enzyme 1a; cET-1, caged ET-1; caged ET-1, [Trp-ODMNB 21 ]ET-1; ET-1, endothelin 1; ET-2, endothelin 2; ET-3, endothelin 3; ETA, endothelin type A receptor; ETB, endothelin type B receptor; ETR, endothelin receptor; GPCR, G protein-coupled receptor; HDAC5; histone deacetylase 5; IP3, inositol 1,4,5-trisphosphate; IP3R, inositol 1,4,5-trisphosphate receptor; ISO, isoproterenol; MEF2, myocyte enhancing factor-2; PBS, phosphate buffered saline; PMSF, phenylmethanesulphonylfluoride; PNGase F, peptide N-glycosidase F; qPCR, quantitative real-time polymerase chain reaction; RNA, ribonucleic acid; RyR, ryanodine receptor; TCA, trichloroacetic acid; TFA, trifluoroacetic acid; TX-100, Triton X-100. Address correspondence to: Bruce G. Allen, Montreal Heart Institute, 5000 Belanger St,. Montréal, Québec, Canada, H1T 1C8., Telephone: (514) ] n whereas extracellular application of ETA and ETB receptor antagonists did not. These data suggest that 1) the endothelin receptor in the cardiac nuclear membranes is ETB, 2) ETB traffic directly to the nuclear membrane after biosynthesis, 3) exogenous endothelins are not ligands for ETB on nuclear membranes, and 4) ETB associated with the nuclear membranes regulate nuclear Ca 2+ signalling.

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“…oxLDL is generated by auto-oxidation in the presence of transition metals (3,4), by cell-mediated mechanisms (5-7), and by enzyme-mediated mechanisms (8 -11). It induces the early changes of atherosclerosis: the expression of adhesion molecules on endothelial cells (12), a decrease in production of endothelial cell-derived relaxing factor (13) and prostacyclin (14), the transformation of macrophages and smooth muscle cells to foam cells (15), the production of various proinflammatory cytokines and growth factors by almost all vascular cells (16,17), the proliferation and migration of vascular cells (18 -20), the retardation of endothelial regeneration (21), and changes in the balance between procoagulant and anticoagulant activity on the vascular cell surface (22). These changes consequently trigger a series of cellular responses in the arterial wall that result in the formation of atheromatous lesions.…”

Section: Oxidized Low Density Lipoprotein (Oxldl)mentioning

confidence: 99%

Oxidized Low Density Lipoprotein Induces Apoptosis in Cultured Human Umbilical Vein Endothelial Cells by Common and Unique Mechanisms

Harada‐Shiba¹,

Kinoshita²,

Kamido³

et al. 1998

Journal of Biological Chemistry

239

147

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Oxidized low density lipoprotein (oxLDL) induces apoptosis in vascular cells. To elucidate the mechanisms involved in this apoptosis, we studied the apoptosisinducing activity in lipid fractions of oxLDL and the roles of two common mechanisms, ceramide generation and the activation of caspases, in apoptosis in human umbilical vein endothelial cells treated with oxLDL. We also studied the effects of antioxidants and cholesterol. oxLDL induced endothelial apoptosis in a time-and dosedependent fashion. Apoptosis-inducing activity was recovered in the neutral lipid fraction of oxLDL. Various oxysterols in this fraction induced endothelial apoptosis. Neither the phospholipid fraction nor its component lysophosphatidylcholine induced apoptosis. ox-LDL induced ceramide accumulation temporarily at 15 min in a dose-dependent fashion. Two inhibitors of acid sphinogomyelinase inhibited both the increase in ceramide and the apoptosis induced by oxLDL. Furthermore, a membrane-permeable ceramide (C 2 -ceramide) induced endothelial apoptosis. These findings demonstrated that ceramide generation by acid sphingomyelinase is indispensable for the endothelial apoptosis induced by oxLDL. Inhibitors of both caspase-1 and caspase-3 inhibited the apoptosis, suggesting that oxLDL induced apoptosis by activating these cysteine proteases. The antioxidants butylated hydroxytoluene and superoxide dismutase but not catalase inhibited the apoptosis induced by oxLDL or 25-hydroxycholesterol. This suggests not only that superoxide plays an important role but also that a critical interaction between oxLDL and the cell takes place on the outer surface of the membrane, because superoxide dismutase is not membrane-permeable. Exogenous cholesterol also inhibited the apoptosis. Our study demonstrated that neutral lipids in oxLDL induce endothelial apoptosis by activating membrane sphingomyelinase in a superoxidedependent manner, as well as by activating caspases.

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Chronic exposure of cultured bovine endothelial cells to oxidized LDL abolishes prostacyclin release.

Cited by 49 publications

References 20 publications

Modulation of vascular tone by low density lipoproteins: effects on L‐arginine transport and nitric oxide synthesis

Modulation of vascular tone by low density lipoproteins: effects on L‐arginine transport and nitric oxide synthesis

Intracrine endothelin signaling evokes IP3-dependent increases in nucleoplasmic Ca2+ in adult cardiac myocytes

Oxidized Low Density Lipoprotein Induces Apoptosis in Cultured Human Umbilical Vein Endothelial Cells by Common and Unique Mechanisms

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