Reduced Expression of Endothelial Nitric Oxide Synthase in the Lungs of Patients with Pulmonary Hypertension

Giaid, Adel; Saleh, Dina

doi:10.1056/nejm199507273330403

Cited by 1,238 publications

(756 citation statements)

References 31 publications

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“…We studied the role of NO in compensatory lung growth at various time points ranging from 0 to 14 days postpneumonectomy utilizing eNOSϪ/Ϫ mice. In the lung, eNOS has been detected in both airway epithelial cells and endothelial cells where it is partly responsible for providing basal pulmonary vascular tone (6). We first sought to measure changes in eNOS protein expression in response to pneumonectomy.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of compensatory lung growth in endothelial nitric oxide synthase-deficient mice

Leuwerke

Kaza

Tribble

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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Pneumonectomy results in rapid compensatory growth of the remaining lung and also leads to increased flow and shear stress, which are known to stimulate endothelial nitric oxide synthase (eNOS). Nitric oxide is an essential mediator of vascular endothelial growth factor-induced angiogenesis, which should necessarily occur during compensatory lung growth. Thus our hypothesis is that eNOS is critical for compensatory lung growth. To test this, left pneumonectomy was performed in eNOS-deficient mice (eNOS−/−), and compensatory growth of the right lung was characterized throughout 14 days postpneumonectomy and compared with wild-type pneumonectomy and sham controls. Compensatory lung growth was severely impaired in eNOS−/− mice, as demonstrated by significant reductions in lung weight index, lung volume index, and volume of respiratory region. Also, pneumonectomy-induced increases in alveolar surface density and cell proliferation were prevented in eNOS−/− mice, indicating that eNOS plays a role in alveolar hyperplasia. Compensatory lung growth was also impaired in wild-type mice treated with the nitric oxide synthase inhibitor N G-nitro-l-arginine methyl ester. Together, these results indicate that eNOS is critical for compensatory lung growth.

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Section: Discussionmentioning

confidence: 99%

Inhibition of compensatory lung growth in endothelial nitric oxide synthase-deficient mice

Leuwerke

Kaza

Tribble

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…This dysfunction provides the basis for further changes in vascular structure and function induced by additional factors. There is emerging evidence that the initial event in the natural history of PAH in COPD could be endothelial injury by cigarette-smoke products with the subsequent down regulation of endothelial nitric oxide synthase and prostacyclin synthase expression and the impairment of endothelial function [103]. When the disease progresses, sustained hypoxaemia and inflammation may induce further pulmonary vascular remodelling, thereby amplifying the initial effects of cigarette smoke [104].…”

Section: Pulmonary Arterial Hypertensionmentioning

confidence: 99%

Systemic manifestations and comorbidities of COPD

Barnes¹,

Celli²

2009

Eur Respir J

1,476

1,113

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Increasing evidence indicates that chronic obstructive pulmonary disease (COPD) is a complex disease involving more than airflow obstruction. Airflow obstruction has profound effects on cardiac function and gas exchange with systemic consequences. In addition, as COPD results from inflammation and/or alterations in repair mechanisms, the ''spill-over'' of inflammatory mediators into the circulation may result in important systemic manifestations of the disease, such as skeletal muscle wasting and cachexia. Systemic inflammation may also initiate or worsen comorbid diseases, such as ischaemic heart disease, heart failure, osteoporosis, normocytic anaemia, lung cancer, depression and diabetes. Comorbid diseases potentiate the morbidity of COPD, leading to increased hospitalisations, mortality and healthcare costs. Comorbidities complicate the management of COPD and need to be evaluated carefully. Current therapies for comorbid diseases, such as statins and peroxisome proliferator-activated receptor-agonists, may provide unexpected benefits for COPD patients. Treatment of COPD inflammation may concomitantly treat systemic inflammation and associated comorbidities. However, new broad-spectrum anti-inflammatory treatments, such as phosphodiesterase 4 inhibitors, have significant side-effects so it may be necessary to develop inhaled drugs in the future. Another approach is the reversal of corticosteroid resistance, for example with effective antioxidants. More research is needed on COPD comorbidities and their treatment.

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“…These lesions have decreased expression of anti-remodeling mediators such as nitric oxide synthase [35] and prostacyclin synthase [36], and tumor suppressors, such as caveolin-1 [37]. These phenotypic characteristics lead us to propose that the plexiform lesions have characteristics in common with neoplasms [38].…”

Section: Pathobiologymentioning

confidence: 99%

Pathology of Pulmonary Hypertension

Tuder

Marecki

Richter

et al. 2013

Clinics in Chest Medicine

220

107

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Reduced Expression of Endothelial Nitric Oxide Synthase in the Lungs of Patients with Pulmonary Hypertension

Abstract: Pulmonary hypertension is associated with diminished expression of endothelial nitric oxide synthase. It is possible that decreased expression of nitric oxide synthase may contribute to pulmonary vasoconstriction and to the excessive growth of the tunica media observed in this disease.

Cited by 1,238 publications

References 31 publications

Inhibition of compensatory lung growth in endothelial nitric oxide synthase-deficient mice

Inhibition of compensatory lung growth in endothelial nitric oxide synthase-deficient mice

Systemic manifestations and comorbidities of COPD

Pathology of Pulmonary Hypertension

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