Endothelin-1 Induces NAD(P)H Oxidase in Human Endothelial Cells

Duerrschmidt, Nicole; Wippich, Nico; Göettsch, Winfried; Broemme, Hans-Juergen; Morawietz, Henning

doi:10.1006/bbrc.2000.2354

Cited by 223 publications

(136 citation statements)

References 27 publications

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“…Many different agonists have been shown to induce endothelial NADPH oxidase activity, including hemodynamic forces (32)(33)(34), VEGF (21,22,24), angiopoietin-1 (Ang1) (21,35,36), tumor necrosis factor-␣ (37), thrombin (38), angiotensin II (37,39), endothelin-1 (40), transforming growth factor-␤ (41), oxidized low density lipoprotein (27), and high potassium (42). Activation of NADPH oxidase is mediated by post-translational modification and/or increased transcription of the regulatory subunits.…”

Section: Vascular Endothelial Growth Factor (Vegf)mentioning

confidence: 99%

NADPH Oxidase Activity Selectively Modulates Vascular Endothelial Growth Factor Signaling Pathways

Abid¹,

Spokes²,

Shih

et al. 2007

Journal of Biological Chemistry

138

125

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Vascular endothelial growth factor (VEGF) and reactive oxygen species (ROS) play critical roles in vascular physiology and pathophysiology. We have demonstrated previously that NADPH oxidase-derived ROS are required for VEGF-mediated migration and proliferation of endothelial cells. The goal of this study was to determine the extent to which VEGF signaling is coupled to NADPH oxidase activity. Human umbilical vein endothelial cells and/or human coronary artery endothelial cells were transfected with short interfering RNA against the p47 phox subunit of NADPH oxidase, treated in the absence or presence of VEGF, and assayed for signaling, gene expression, and function. We show that NADPH oxidase activity is required for VEGF activation of phosphoinositide 3-kinase-Akt-forkhead, and p38 MAPK, but not ERK1/2 or JNK. The permissive role of NADPH oxidase on phosphoinositide 3-kinase-Akt-forkhead signaling is mediated at post-VEGF receptor levels and involves the nonreceptor tyrosine kinase Src. DNA microarrays revealed the existence of two distinct classes of VEGF-responsive genes, one that is ROS-dependent and another that is independent of ROS levels. VEGF-induced, thrombomodulin-dependent activation of protein C was dependent on NADPH oxidase activity, whereas VEGF-induced decay-accelerating factor-mediated protection of endothelial cells against complement-mediated lysis was not. Taken together, these findings suggest that NADPH oxidase-derived ROS selectively modulate some but not all the effects of VEGF on endothelial cell phenotypes.

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Section: Vascular Endothelial Growth Factor (Vegf)mentioning

confidence: 99%

NADPH Oxidase Activity Selectively Modulates Vascular Endothelial Growth Factor Signaling Pathways

Abid¹,

Spokes²,

Shih

et al. 2007

Journal of Biological Chemistry

138

125

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“…In addition, ET-1 (a vasoconstrictor peptide secreted from endothelial cell) is thought to play a pathological role in a number of vascular diseases (Goto et al, 1996). Interestingly, it was recently reported that ET-1 can activate PI3-K in several cells (Ishibashi et al, 2000;Kawanabe et al, 2003) and that ET-1 activates NAD(P)H oxidase and induces superoxide production in cultured endothelial and smooth muscle cells (Duerrschmidt et al, 2000;Wedgwood et al, NAD(P)H oxidase is increased in STZ-induced diabetic aortae (Kanie and Kamata, 2002) and that this increase is normalized by the endothelin antagonist, J-104132, suggesting that ET-1 is involved in the increased formation of superoxide anions. Furthermore, we found that chronic administration of a relatively low dose of bezafibrate, which was insufficient to alter the levels of plasma lipids (including total cholesterol, LDL cholesterol, high density lipoprotein (HDL) cholesterol, and triglyceride), exerted an improvement effect on the endothelial dysfunction seen in the aorta in rats with established STZ-induced diabetes.…”

Section: Mechanisms Underlying Impaired Endothelial Function In Diabementioning

confidence: 99%

The PI3-K/Akt pathway: roles related to alterations in vasomotor responses in diabetic models

Kobayashi

Matsumoto

Kamata

2005

J Smooth Muscle Res

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Macro-and microvascular disease states currently represent the principal causes of morbidity and mortality in patients with type I or type II diabetes mellitus. Abnormal vasomotor responses and impaired endothelium-dependent vasodilation have been demonstrated in various beds in different animal models of diabetes and in humans with type I or type II diabetes. Several mechanisms leading to endothelial dysfunction have been reported, including changes in substrate avail ability, impaired release of NO, and increased destruction of NO. The principal mediators of diabetes-associated endothelial dysfunction are (a) increases in oxidized low density lipoprotein, endothelin-1, angiotensin II, oxidative stress, and (b) decreases in the actions of insulin or growth factors in endothelial cells. An accumulating body of evidence indicates that abnormal regulation of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway may be one of several factors contributing to vascular dysfunction in diabetes. The PI3-K pathway, which activates serine/threonine protein kinase Akt, enhances NO synthase phosphorylation and NO production. Several studies suggest that in diabetes the relative ineffectiveness of insulin and the hyperglycemia act together to reduce activity in the insulin-receptor substrates (IRS)/PI3-K/Akt pathway, resulting in impairments of both IRS/PI3-K/Akt-mediated endothelial function and NO production. This article summarizes the PI3-K/Akt pathway-mediated contraction and relaxation responses induced by various agents in the blood vessels of diabetic animals.

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“…15 ET A receptors play an important role in the development of DOCA-salt-induced hypertension, whereas ET B receptors may protect against vascular and renal injuries in this model. 16 ET-1 is able to activate NADPH oxidase in endothelial cells 17 and stimulates O 2 Ϫ production in pulmonary smooth muscle cells. 18 Therefore, we hypothesized that ET-1 activates NADPH oxidase to produce vascular O 2 Ϫ in DOCA-salt hypertensive rats.…”

mentioning

confidence: 99%

Endothelin-1 Increases Vascular Superoxide via Endothelin _A –NADPH Oxidase Pathway in Low-Renin Hypertension

Fink²,

Watts³

et al. 2003

Circulation

305

269

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Background-Angiotensin II-induced hypertension is associated with NAD(P)H oxidase-dependent superoxide production in the vessel wall. Vascular superoxide level is also increased in deoxycorticosterone acetate (DOCA)-salt hypertension, which is associated with a markedly depressed plasma renin activity because of sodium retention. However, the mechanisms underlying superoxide production in low-renin hypertension are undefined. Methods and Results-This study investigated (1) whether and how endothelin-1 (ET-1), which is increased in DOCA-salt hypertensive rats, contributes to arterial superoxide generation and (2) the effect of gene transfer of manganese superoxide dismutase and endothelial nitric oxide synthase. Both superoxide and ET-1 levels were significantly elevated in carotid arteries of DOCA-salt rats compared with that of the sham-operated controls. ET-1 concentration-dependently stimulated superoxide production in vitro in carotid arteries of normotensive rats. The increase in arterial superoxide in both ET-1-treated normotensive and DOCA-salt rats was reversed by a selective ET A receptor antagonist, ABT-627, the flavoprotein inhibitor diphenyleneiodonium, and the NADPH oxidase inhibitor apocynin but not by the nitric oxide synthase inhibitor N -L-arginine methyl ester or the xanthine oxidase inhibitor allopurinol. Furthermore, in vivo blockade of ET A receptors significantly reduced arterial superoxide levels, with a concomitant decrease of systolic blood pressure in DOCA-salt rats. Ex vivo gene transfer of manganese superoxide dismutase or endothelial nitric oxide synthase also suppressed superoxide levels in carotid arteries of DOCA-salt rats. Conclusions-These findings suggest that ET-1 augments vascular superoxide production at least in part via an ET A /NADPH oxidase pathway in low-renin mineralocorticoid hypertension.

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Endothelin-1 Induces NAD(P)H Oxidase in Human Endothelial Cells

Cited by 223 publications

References 27 publications

NADPH Oxidase Activity Selectively Modulates Vascular Endothelial Growth Factor Signaling Pathways

NADPH Oxidase Activity Selectively Modulates Vascular Endothelial Growth Factor Signaling Pathways

The PI3-K/Akt pathway: roles related to alterations in vasomotor responses in diabetic models

Endothelin-1 Increases Vascular Superoxide via Endothelin _A –NADPH Oxidase Pathway in Low-Renin Hypertension

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Endothelin-1 Induces NAD(P)H Oxidase in Human Endothelial Cells

Cited by 223 publications

References 27 publications

NADPH Oxidase Activity Selectively Modulates Vascular Endothelial Growth Factor Signaling Pathways

NADPH Oxidase Activity Selectively Modulates Vascular Endothelial Growth Factor Signaling Pathways

The PI3-K/Akt pathway: roles related to alterations in vasomotor responses in diabetic models

Endothelin-1 Increases Vascular Superoxide via Endothelin A –NADPH Oxidase Pathway in Low-Renin Hypertension

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Endothelin-1 Increases Vascular Superoxide via Endothelin _A –NADPH Oxidase Pathway in Low-Renin Hypertension