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Current Drug Metabolism


ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

Dysfunction of Pulmonary Vascular Endothelium in Chronic Obstructive Pulmonary Disease: Basic Considerations for Future Drug Development

Author(s): Qin Yang, Malcolm J. Underwood, Michael K.Y. Hsin, Xiao-Cheng Liu and Guo-Wei He

Volume 9, Issue 7, 2008

Page: [661 - 667] Pages: 7

DOI: 10.2174/138920008785821684

Price: $65


Chronic obstructive pulmonary disease (COPD) is one of the leading health problems worldwide and continues to be a major cause of morbidity and mortality in developed countries. The clinical features of COPD are chronic obstructive bronchiolitis and emphysema. Pulmonary vascular endothelial dysfunction is a characteristic pathological finding of COPD at different stages of the disease. Functional changes of pulmonary endothelial cells in COPD include antiplatelet abnormalities, anticoagulant disturbances, endothelial activation, atherogenesis, and compromised regulation of vascular tone which may adversely affect the ventilation-perfusion match in COPD. As the most important risk factor of COPD, cigarette smoking may initiate pulmonary vascular impairment through direct injury of endothelial cells or release of inflammatory mediators. Morphological changes such as denudation of endothelium and endothelial cell apoptosis have been observed in the pulmonary vasculature in COPD patients as well as functional alterations. Changes in the expression of tissue factor pathway inhibitor (TFPI), thrombomodulin, selectins, and adhesion molecules in pulmonary endothelial cells as well as complex regulation and interaction of vasoactive substances and growth factors released from endothelium may underlie the mechanisms of pulmonary endothelial dysfunction in COPD. The mechanism of endothelial repair/regeneration in COPD, although not fully understood, may involve upregulation of vascular endothelial growth factors in the early stages along with an increased number of bone marrow- derived progenitor cells. These factors should be taken into account when developing new strategies for the pharmacological therapy of patients with COPD.

Keywords: Chronic obstructive pulmonary disease, pulmonary endothelium, adhesion molecules, endothelium-derived relaxing factors, VEGF, vascular progenitor cells

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