NADPH oxidase mediates angiotensin II-induced endothelin-1 expression in vascular adventitial fibroblasts

An, Sheng Jun; Boyd, Ryan; Zhu, Min; Chapman, Alexander; Pimentel, David R.; Wang, Hui Di

doi:10.1016/j.cardiores.2007.02.015

Cited by 72 publications

(45 citation statements)

References 51 publications

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“…Recently, it has been reported that Ang II stimulation evokes expression of ET-1 in adventitial fibroblasts contributes to type I procollagen expression through activation of ET A receptors, suggesting a functional role for adventitial ET-1 release in the regulation of the extracellular matrix [15] . Expression of ET-1 in adventitial fibroblasts is mediated by ·O 2 - [16] , consistent with the findings in many different cell types [17] , including VSM [18,19] . However, the mechanisms of oxidative stress regulating ET-1 production are still unclear.…”

Section: Perivascular Fibroblasts: Source Of Ros and Regulation Of Vasupporting

confidence: 89%

New perspectives on vascular wall signaling: role of perivascular adipocytes and fibroblasts

Kwan

Hsieh

et al. 2010

Acta Pharmacol Sin

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Section: Perivascular Fibroblasts: Source Of Ros and Regulation Of Vasupporting

confidence: 89%

New perspectives on vascular wall signaling: role of perivascular adipocytes and fibroblasts

Kwan

Hsieh

et al. 2010

Acta Pharmacol Sin

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“…Indeed, over-expression of SOD in mouse aortic adventitial fibroblasts inhibits the ANG IIinduced type I procollagen α-I protein expression and . O 2 -generation [188].…”

Section: Ang Ii-induced Collagen Production and Degradation During Inmentioning

confidence: 99%

Modulation of Reactive Oxygen Species and Collagen Synthesis by Angiotensin II in Cardiac Fibroblasts

Lijnen¹

2011

TOHYPERJ

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Angiotensin II increases the NAD(P)H-dependent superoxide anion production and the intracellular generation of reactive oxygen species in cardiac fibroblasts and apocynin, a NAD(P)H oxidase inhibitor, abrogates this rise. The membrane associated NAD(P)H oxidase complex is the predominant source of superoxide anion and reactive oxygen species generation in angiotensin II-stimulated adult cardiac fibroblasts. Inhibition of this NAD(P)H oxidase complex with apocynin completely blocks the angiotensin II-stimulated collagen production, collagen I and III protein and mRNA expression.Superoxide anion production is also increased by the Cu,Zn-superoxide dismutase (SOD) inhibitor diethyldithiocarbamic acid (DETC) and decreased by the superoxide scavenger tempol in control and ANG II-treated fibroblasts. ANG II and DETC stimulate the collagen production and the collagen I and fibronectin content in fibroblasts. The SOD mimetics tempol and EUK-8 as well as polyethyleneglycol-SOD reduce the collagen production.ANG II also decreases the activity and mRNA and protein expression of the mitochondrial antioxidants Mn-SOD and peroxiredoxin-3. Upon phosphorylation of Akt by ANG II, P-Akt is translocated from the cytoplasm to the nucleus and nuclear phosphorylation of FOXO3a by P-Akt leads to relocalisation of FOXO3a from the nucleus to the cytosol, resulting in a decrease in its transcriptional activity and in Mn-SOD expression. These data indicate that ANG II inactivates FOXO3a by activating Akt and this leads to a reduction in the expression of the antioxidant Mn-SOD. A role of SOD and the formed reactive oxygen species in the regulation and organization of collagen in cardiac fibroblasts is suggested.

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“…10 -12 Apart from inducing vasoconstriction, ET-1 activates vascular NADPH oxidase, leading to an increase in oxidative stress through enhanced reactive oxygen species (ROS) production. 13,14 Because oxidative stress is generally increased in hypertension and plays a pathogenic role in the development and progression of cardiovascular disease, we hypothesized that enhanced formation of ROS contributes to the sunitinib-induced cardiovascular adverse effects. 15 To further explore the cardiovascular adverse effects of sunitinib, we performed detailed studies in chronically instrumented awake swine.…”

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confidence: 99%

Sunitinib-Induced Systemic Vasoconstriction in Swine Is Endothelin Mediated and Does Not Involve Nitric Oxide or Oxidative Stress

et al. 2012

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Abstract-Angiogenesis inhibition with agents targeting tyrosine kinases of vascular endothelial growth factor receptors is an established anticancer treatment, but is, unfortunately, frequently accompanied by systemic hypertension and cardiac toxicity. Whether vascular endothelial growth factor receptor antagonism also has adverse effects on the pulmonary and coronary circulations is presently unknown. In chronically instrumented awake swine, the effects of the vascular endothelial growth factor receptor antagonist sunitinib on the systemic, pulmonary, and coronary circulation were studied. One week after sunitinib (50 mg PO daily), mean aortic blood pressure (MABP) had increased from 83Ϯ5 mm Hg at baseline to 97Ϯ6 mm Hg (PϽ0.05) because of a 57Ϯ20% increase in systemic vascular resistance as cardiac output decreased. In contrast, sunitinib had no discernible effects on pulmonary and coronary hemodynamics or cardiac function. We subsequently investigated the mechanisms underlying the sunitinib-induced systemic hypertension. Intravenous administration of NO synthase inhibitor N G -nitro-L-arginine increased MABP by 24Ϯ1 mm Hg under baseline conditions, whereas it increased MABP even further after sunitinib administration (32Ϯ3 mm Hg; PϽ0.05). Reactive oxygen species scavenging with a mixture of antioxidants lowered MABP by 13Ϯ2 mm Hg before but only by 5Ϯ2 mm Hg (PϽ0.05) after sunitinib administration. However, intravenous administration of the dual endothelin A/endothelin B receptor blocker tezosentan, which did not lower MABP at baseline, completely reversed MABP to presunitinib values. These findings indicate that sunitinib produces vasoconstriction selectively in the systemic vascular bed, without affecting pulmonary or coronary circulations. The sunitinib-mediated systemic hypertension is principally attributed to an increased vasoconstrictor influence of endothelin, with no apparent contributions of a loss of NO bioavailability or increased oxidative stress. (Hypertension. 2012;59:151-157.) Key Words: endothelin 1 Ⅲ hypertension Ⅲ oxidative stress Ⅲ pulmonary hypertension Ⅲ vascular endothelial growth factor A ngiogenesis inhibition, by targeting the tyrosine kinases of the vascular endothelial growth factor (VEGF) receptors (VEGFRs), has become an established treatment of several tumor types. This therapy is associated with adverse effects, including the development of hypertension and cardiac and renal toxicity. 1 Hypertension has been reported in Յ60% of patients treated with sunitinib, an orally active multitarget receptor tyrosine kinase inhibitor (RTKI), targeting, among others, the VEGFR-1 and -2, which is used as first-line treatment of metastatic renal cell carcinoma or imatinib-resistant gastrointestinal stromal tumors. 1 In addition, impaired cardiac function, as reflected by a decrease in left ventricular ejection fraction of 10% to 15%, has been observed in Յ28% of patients treated with sunitinib. 2 Angina pectoris and increased levels of biomarkers reflecting ischemic myocardial damage may als...

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NADPH oxidase mediates angiotensin II-induced endothelin-1 expression in vascular adventitial fibroblasts

Cited by 72 publications

References 51 publications

New perspectives on vascular wall signaling: role of perivascular adipocytes and fibroblasts

New perspectives on vascular wall signaling: role of perivascular adipocytes and fibroblasts

Modulation of Reactive Oxygen Species and Collagen Synthesis by Angiotensin II in Cardiac Fibroblasts

Sunitinib-Induced Systemic Vasoconstriction in Swine Is Endothelin Mediated and Does Not Involve Nitric Oxide or Oxidative Stress

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