Chronic lung allograft rejection and airway microvasculature: Is HIF-1 the missing link?

Chronic lung allograft rejection, known as obliterative bronchiolitis (OB), is the leading cause of death in lung transplant patients. Although OB pathogenesis is not fully understood, in this issue of the JCI, Jiang and colleagues report that tissue hypoxia resulting in dysfunctional airway microvasculature precedes the airway fibrosis characteristic of OB. In addition, a relative deficiency of allograft endothelial cell-derived HIF-1 alpha contributes to this process. Data showing that overexpressing HIF-1 alpha restores the microvascular airway normoxia and prevents airway fibrosis highlight a novel role for vascular biology in OB pathogenesis.