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Enhanced Expression of Vascular Endothelial Growth Factor in Pulmonary Arteries of Smokers and Patients with Moderate Chronic Obstructive Pulmonary Disease

Departments of Pulmonary Medicine and Pathology, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic
Universitat de Barcelona, Barcelona, Spain

Correspondence and requests for reprints should be addressed to Dr. Joan A. Barberà, Servei de Pneumologia, Hospital Clínic, Villarroel, 170, 08036 Barcelona, Spain. E-mail: jbarbera{at}clinic.ub.es

Chronic obstructive pulmonary disease (COPD) is associated with structural and functional changes in the pulmonary circulation that commence at an early stage. To investigate whether vascular endothelial growth factor (VEGF) might be implicated as a mediator in COPD-associated pulmonary vascular changes, we studied surgical specimens obtained from 19 nonsmokers, 21 smokers with normal lung function, 28 patients with moderate COPD, and 10 patients with severe emphysema. The expression of VEGF in pulmonary muscular arteries was evaluated by immunohistochemistry, its protein content in lung tissue by Western blot analysis, and VEGF mRNA and its isoforms were analyzed by reverse transcription-polymerase chain reaction. The immunohistochemical expression of VEGF was increased in pulmonary arteries of smokers (median, 68% [interquartile range, 60–88]) and patients with moderate COPD (77% [63–82]), compared with nonsmokers (53% [40–63]) (p < 0.05 each). The expression of VEGF in smooth muscle cells correlated with the thickness of the vessel wall (r = 0.38, p < 0.01). VEGF protein content in lung tissue was reduced in severe emphysema, where reverse transcription-polymerase chain reaction demonstrated a lower proportion of the VEGF₁₈₉ isoform. In conclusion, the expression of VEGF varies according to the severity of COPD and might be involved in the pathogenesis of pulmonary vascular remodeling at early stages of the disease.

Key Words: chronic obstructive pulmonary disease • cigarette smoking • pulmonary artery • endothelium • vascular endothelial growth factor

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