Angiogenesis, Lymphangiogenesis, and Inflammation in Chronic Obstructive Pulmonary Disease (COPD): Few Certainties and Many Outstanding Questions

: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation, predominantly affecting the lung parenchyma and peripheral airways, that results in progressive and irreversible airflow obstruction. COPD development is promoted by persistent pulmonary inflammation in response to several stimuli (e.g., cigarette smoke, bacterial and viral infections, air pollution, etc.). Angiogenesis, the formation of new blood vessels, and lymphangiogenesis, the formation of new lymphatic vessels, are features of airway inflammation in COPD. There is compelling evidence that effector cells of inflammation (lung-resident macrophages and mast cells and infiltrating neutrophils, eosinophils, basophils, lymphocytes, etc.) are major sources of a vast array of angiogenic (e.g., vascular endothelial growth factor-A (VEGF-A), angiopoietins) and/or lymphangiogenic factors (VEGF-C, -D). Further, structural cells, including bronchial and alveolar epithelial cells, endothelial cells, fibroblasts/myofibroblasts, and airway smooth muscle cells, can contribute to inflammation and angiogenesis in COPD. Although there is evidence that alterations of angiogenesis and, to a lesser extent, lymphangiogenesis, are associated with COPD, there are still many unanswered questions.