Physiological and pathological angiogenesis in the adult pulmonary circulation

Angiogenesis occurs during growth and physiological adaptation in many systemic organs, for example, exercise-induced skeletal and cardiac muscle hypertrophy, ovulation, and tissue repair. Disordered angiogenesis contributes to chronic inflammatory disease processes and to tumor growth and metastasis. Although it was previously thought that the adult pulmonary circulation was incapable of supporting new vessel growth, over that past 10 years new data have shown that angiogenesis within this circulation occurs both during physiological adaptive processes and as part of the pathogenic mechanisms of lung diseases. Here we review the expression of vascular growth factors in the adult lung, their essential role in pulmonary vascular homeostasis and the changes in their expression that occur in response to physiological challenges and in disease. We consider the evidence for adaptive neovascularization in the pulmonary circulation in response to alveolar hypoxia and during lung growth following pneumonectomy in the adult lung. In addition, we review the role of disordered angiogenesis in specific lung diseases including idiopathic pulmonary fibrosis, acute adult distress syndrome and both primary and metastatic tumors of the lung. Finally, we examine recent experimental data showing that therapeutic enhancement of pulmonary angiogenesis has the potential to treat lung diseases characterized by vessel loss.