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Pulmonary vascular involvement in chronic obstructive pulmonary disease

Pulmonary Hypertension Center and Dept of Pathology, University of Colorado, Health Sciences Center, Denver, Colorado, USA

CORRESPONDENCE: N.F. Voelkel, Division of Pulmonary Sciences and Critical Care Medicine, 4200 E. Ninth Avenue, C272, Denver, CO 80262. Fax: 1 303 3155632. E-mail: norbert.voelkel@uchsc.edu

Keywords: apoptosis, chronic obstructive pulmonary disease, emphysema, lung vascular remodelling, oxidative stress, vascular endothelial growth factor

Received: June 30, 2003
Accepted June 30, 2003

Chronic obstructive lung disease affects the entire lung, not just the airways. Although pulmonary hypertension (PH) has long been recognised in a subset of patients with COLD, the important pathophysiological questions remain unanswered. Oxygen supplementation, however, has been shown to blunt the exercise-induced PH in these patients. Hypercoagulability has also been described in patients with COLD. This may, in part, be due to the inflammatory aspects of COLD exacerbation events. In addition to perivascular inflammation, the pathology of vessels in COLD includes intimal thickening, muscularisation of arterioles, in situ thrombosis, loss of capillaries and precapillary arterioles, and vascular congestion and stasis. Recent work describes apoptosis of septal endothelial cells and decreased expression of vascular endothelial growth factor (VEGF) and one of its receptors, VEGFRII, in lungs from patients with emphysema. Based on this work, a rat model was developed that shows chronic blockade of VEGF receptors leads to septal cell apoptosis and results in emphysema and PH. This animal model has led to prevention trials using 1) a broad-spectrum caspase inhibitor, 2) a superoxide dismutase mimetic, and 3) ₁-antitrypsin.

These findings highlight the importance of vascular endothelial growth factor, apoptosis, oxidative stress and protease activity in the pathogenesis of emphysema. They also underscore the importance of the vasculature in what is traditionally thought of as an airways disease. Future treatment strategies need to address the vascular components of chronic obstructive lung disease.

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