Abstract
Pulmonary hypertension is a prevalent complication of chronic obstructive pulmonary disease (COPD) that is associated with poor prognosis. Although pulmonary hypertension is usually diagnosed in patients with advanced disease, changes in pulmonary vessels are already apparent at early disease stages, and in smokers without airflow obstruction. Changes in pulmonary vessels include intimal hyperplasia, resulting from proliferating mesenchymal cells, and elastic and collagen deposition as well as endothelial dysfunction. Dysregulation of endothelium-derived mediators and growth factors and inflammatory mechanisms underlie the endothelial dysfunction and vessel remodeling. Circumstantial and experimental evidence suggests that cigarette smoke products can initiate pulmonary vascular changes in COPD and that, at advanced disease stages, hypoxia may amplify the effects of cigarette smoke on pulmonary arteries. Bone marrow-derived progenitor cells may contribute to vessel repair and to vessel remodeling, a process that appears to be facilitated by transforming growth factor-β.