Abstract | RATIONALE: OBJECTIVES: To test whether NEP activity and expression are reduced in COPD lungs and pulmonary arterial smooth muscle cells (SMCs) exposed to cigarette smoke extract or hypoxia and begin to investigate mechanisms involved. METHODS: MEASUREMENTS AND MAIN RESULTS:
COPD lungs demonstrated areas of vascular rarification, distal muscularization, and variable intimal and prominent medial/adventitial thickening. NEP activity was reduced by 76%; NEP protein expression was decreased in alveolar walls and distal vessels; mRNA expression was also decreased. In SMCs exposed to cigarette smoke extract, hypoxia, and H₂O₂, NEP activity and expression were also reduced. Reactive oxygen species inactivated NEP activity; NEP protein degradation appeared to be substantially induced. CONCLUSIONS: Mechanisms responsible for reduced NEP activity and protein expression include oxidative reactions and protein degradation. Maintaining or increasing lung NEP may protect against pulmonary vascular remodeling in response to chronic smoke and hypoxia.
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Authors | Marilee J Wick, Erica J Buesing, Carol A Wehling, Zoe L Loomis, Carlyne D Cool, Martin R Zamora, York E Miller, Sean P Colgan, Louis B Hersh, Norbert F Voelkel, Edward C Dempsey |
Journal | American journal of respiratory and critical care medicine
(Am J Respir Crit Care Med)
Vol. 183
Issue 3
Pg. 330-40
(Feb 01 2011)
ISSN: 1535-4970 [Electronic] United States |
PMID | 20813891
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
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Topics |
- Adolescent
- Aged
- Airway Remodeling
(physiology)
- Blotting, Western
- Case-Control Studies
- Female
- Humans
- Lung
(blood supply, chemistry, pathology)
- Male
- Middle Aged
- Neprilysin
(analysis, physiology)
- Pulmonary Alveoli
(pathology)
- Pulmonary Artery
(pathology)
- Pulmonary Disease, Chronic Obstructive
(pathology, physiopathology)
- Young Adult
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