Angiogenesis: A potentially critical part of remodelling in chronic airway diseases?

Angiogenesis is a prominent feature of the structural tissue remodelling that occurs in the chronic airway diseases of asthma, Bronchiolitis Obliterans Syndrome (BOS, post-lung transplantation), and in smoking-related Chronic Obstructive Pulmonary Disease (COPD). For each, we have explored the relationship between angiogenesis and underlying chronic inflammatory processes-are the hypervascular changes secondary to inflammation, or do they occur in parallel? What are the likely growth factors which stimulate the angiogenic process? We discuss the relationships that have been studied between angiogenesis and the physiological impairment of airflow obstruction. The pattern that emerges is complex and variable. In asthma, there is strong evidence to suggest that Vascular Endothelial Growth Factor (VEGF) and its receptor system is upregulated in the airway. Local production of VEGF has also been implicated as a major driver of angiogenesis in the airway component of COPD, though paradoxically emphysema seems to be due to lack of VEGF in the lung parenchyma. In BOS, the evidence suggests that VEGF is lacking in the airway: other mediators and especially C-X-C chemokines such as Interleukin (IL)-8, are likely to be more important in angiogenesis. The physiological consequences of angiogenesis are likely to be important in asthma (especially during acute episodes of deterioration), and probably also in COPD, although data is equivocal. In BOS, increased airway vascularity appears to occur early, but is not progressive. In terms of therapy, evidence for anti-angiogenic effectiveness is strongest for Inhaled Corticosteroid (ICS) and Long Acting Beta-Agonists (LABA) in asthma. © 2008.