Function of NADPH Oxidase 1 in Pulmonary Arterial Smooth Muscle Cells After Monocrotaline-Induced Pulmonary Vascular Remodeling

Veit, Florian; Pak, Oleg; Egemnazarov, Bakytbek; Roth, Markus; Kosanovic, Djuro; Seimetz, Michael; Sommer, Natascha; Ghofrani, Hossein Ardeschir; Seeger, Werner; Grimminger, Friedrich; Brandes, Ralf P.; Schermuly, Ralph Theo; Weißmann, Norbert

doi:10.1089/ars.2012.4904

Cited by 63 publications

(58 citation statements)

References 95 publications

(119 reference statements)

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“…Nox1 expression is increased in mouse lung cell lines that are exposed to 72h hyperoxia, while hyperoxia-induced ROS generation and lung injury are attenuated in Nox1-deficient mice (24). Increased pulmonary Nox1 expression was reported in neonatal mice with PH after hyperoxia (17) and in neonatal piglets exposed to hypoxia (42), and Nox1 may be involved in pulmonary vascular remodeling in monocrotaline-treated rats (174). Nox1 levels are unchanged in the lungs of fetal lambs with chronic intrauterine PH (187), although alteration of Nox1 activity in this model is currently unknown.…”

Section: Nadph Oxidasesmentioning

confidence: 98%

“…Cyclin D1 regulates the transition from G 0 /G 1 to S phase in the cell cycle, resulting in the activation of genes that are necessary for cell-cycle progression. Cyclin D1 expression is increased in PPHN lungs and PASMC (187) and in PASMC isolated from monocrotaline-treated rats (174). Nox4 small interfering RNA decreases cyclin D1 expression in PPHN PASMC, and intratracheal catalase decreases cyclin D1 expression in the lungs of ventilated PPHN lambs (187).…”

Section: Nadph Oxidasesmentioning

confidence: 98%

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Role of Reactive Oxygen Species in Neonatal Pulmonary Vascular Disease

Wedgwood

Steinhorn

2014

Antioxidants & Redox Signaling

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Significance: Abnormal lung development in the perinatal period can result in severe neonatal complications, including persistent pulmonary hypertension (PH) of the newborn and bronchopulmonary dysplasia. Reactive oxygen species (ROS) play a substantive role in the development of PH associated with these diseases. ROS impair the normal pulmonary artery (PA) relaxation in response to vasodilators, and ROS are also implicated in pulmonary arterial remodeling, both of which can increase the severity of PH. Recent Advances: PA ROS levels are elevated when endogenous ROS-generating enzymes are activated and/or when endogenous ROS scavengers are inactivated. Animal models have provided valuable insights into ROS generators and scavengers that are dysregulated in different forms of neonatal PH, thus identifying potential therapeutic targets. Critical Issues: General antioxidant therapy has proved ineffective in reversing PH, suggesting that it is necessary to target specific signaling pathways for successful therapy. Future Directions: Development of novel selective pharmacologic inhibitors along with nonantioxidant therapies may improve the treatment outcomes of patients with PH, while further investigation of the underlying mechanisms may enable earlier detection of the disease.

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Section: Nadph Oxidasesmentioning

confidence: 98%

Section: Nadph Oxidasesmentioning

confidence: 98%

Role of Reactive Oxygen Species in Neonatal Pulmonary Vascular Disease

Wedgwood

Steinhorn

2014

Antioxidants & Redox Signaling

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“…It is important to mention that Nox1 upregulation has been suggested to contribute to nonhypoxia-induced PH. 38 Eventually, the cell specificity of ROS formation has an impact on its effects. Nox4 overexpression in SMCs correlates with media hypertrophy, whereas Nox4 overexpression in endothelial cells is not associated with PASMC hyperplasia.…”

mentioning

confidence: 99%

NADPH Oxidase 4 is Not Involved in Hypoxia‐Induced Pulmonary Hypertension

et al. 2016

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“…Thus, in physiological levels, ROS might function as signalling molecules in numerous cellular processes, including differentiation [89], proliferation [128], apoptosis [156], migration [148], secretion [64], regulation of transcription factor expression [30] and adaptation processes, such as HPV [190,202,203]. Pathological excess in ROS production or disproportionate removal of ROS by the cellular antioxidant system causes development of different pathologies [146], including PH [128,179].…”

Section: The Mechanism Of Hpv and Pulmonary Vascular Remodellingmentioning

confidence: 99%

“…The role of NOXs has been addressed in different animal models of PH such as persistent PH of the newborn in foetal lambs [27], chronic intermittent hypoxia-induced PH in mice [151], monocrotaline-induced PH in rats [179] and, importantly, in chronic hypoxia-induced PH in newborn piglets [39] and in mice [112].…”

Section: Noxs and Chronic Hypoxia-induced Pulmonary Hypertensionmentioning

confidence: 99%

NADPH oxidases—do they play a role in TRPC regulation under hypoxia?

Malczyk

Veith

Schermuly

et al. 2015

Pflugers Arch - Eur J Physiol

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In the lung, acute alveolar hypoxia causes hypoxic pulmonary vasoconstriction (HPV) to maintain ventilation perfusion matching and thus optimal oxygenation of blood. In contrast, global chronic hypoxia triggers a pathological thickening of pulmonary arterial walls, called pulmonary vascular remodelling, leading to persistence of pulmonary hypertension (PH). Moreover, ischaemia or hypoxia can lead to a damage of pulmonary endothelial cells with subsequent oedema formation. Alterations in reactive oxygen species (ROS) have been suggested as a crucial mediator of such responses. Among the various sources of cellular ROS production, NADPH oxidases (NOXs) have been found to contribute to these physiological and pathophysiological signalling processes. NOXs are the only known examples that generate ROS as the primary function of the enzyme system. However, the downstream targets of NOX-derived ROS signalling in hypoxia are still not known. Canonical transient receptor potential (TRPC) channels recently have been recognised as directly or indirectly ROS-activated channels and have been shown to be essential for hypoxia-dependent vascular regulatory processes in the lung. Against this background, we here summarise the current knowledge on NOX-mediated TRPC channel signalling during hypoxia in the pulmonary circulation.

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Function of NADPH Oxidase 1 in Pulmonary Arterial Smooth Muscle Cells After Monocrotaline-Induced Pulmonary Vascular Remodeling

Abstract: In contrast to hypoxia-induced PH, Nox1 but not Nox4 is responsible for pathophysiological proliferation and migration of PASMC in an inflammatory model of MCT-induced PH via increased superoxide production. Thus, different Nox isoforms may be targeted in different forms of PH.

Cited by 63 publications

References 95 publications

Role of Reactive Oxygen Species in Neonatal Pulmonary Vascular Disease

Role of Reactive Oxygen Species in Neonatal Pulmonary Vascular Disease

NADPH Oxidase 4 is Not Involved in Hypoxia‐Induced Pulmonary Hypertension

NADPH oxidases—do they play a role in TRPC regulation under hypoxia?

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