Disease Research Area 4 (Emphysema/COPD)
Our group recently found that loss of endothelial cell (EC) hypoxia inducible factor-2α (HIF-2α), induced by cigarette smoke, plays a key role in the development of emphysema. We discovered that deleting EC-derived Hif-2α in adult mice causes EC apoptosis, alveolar microvascular/pericyte destruction, increased inflammation, enlarged alveoli, an obstructive ventilatory defect and decreased hepatocyte growth factor HGF. Gain-of-function EC Hif-2α mice are protected from VEGFR2 inhibitor-induced emphysema. Emphysema affects millions around the world. Current therapies rely largely on symptom mitigation and not on fundamental mechanisms of disease. Our studies provide new insight into the pivotal roles of endothelial HIF-2α in the survival and repair of lung parenchyma and evaluate the possibility of modulating HIFs as potential therapeutic targets in emphysema.