biostudies-literatureJiang XNHLBI NIH HHSNIGMS NIH HHS2336-49https://www.ebi.ac.uk/biostudies/studies/S-EPMC3104770biostudies-literatureUnknown121(6)Chronic rejection, manifested as small airway fibrosis (obliterative bronchiolitis [OB]), is the main obstacle to long-term survival in lung transplantation. Recent studies demonstrate that the airways involved in a lung transplant are relatively hypoxic at baseline and that OB pathogenesis may be linked to ischemia induced by a transient loss of airway microvasculature. Here, we show that HIF-1α mediates airway microvascular repair in a model of orthotopic tracheal transplantation. Grafts with a conditional knockout of Hif1a demonstrated diminished recruitment of recipient-derived Tie2⁺ angiogenic cells to the allograft, impaired repair of damaged microvasculature, accelerated loss of microvascular perfusion, and hastened denudation of epithelial cells. In contrast, graft HIF-1α overexpreThe Journal of clinical investigationAdenovirus-mediated HIF-1α gene transfer promotes repair of mouse airway allograft microvasculature and attenuates chronic rejection.PMC3104770R01 HL082662P01 HL108797HL055338R56 HL082662R01 HL055338P20 GM078494GM078494HL095686R01 HL095686HL082662Tian WNicolls MRJiang XSemenza GLBeilke JNatarajan RKhan MAKosek JYoder MCfalseAdenovirus-mediated HIF-1α gene transfer promotes repair of mouse airway allograft microvasculature and attenuates chronic rejection.Chronic rejection, manifested as small airway fibrosis (obliterative bronchiolitis [OB]), is the main obstacle to long-term survival in lung transplantation. Recent studies demonstrate that the airways involved in a lung transplant are relatively hypoxic at baseline and that OB pathogenesis may be linked to ischemia induced by a transient loss of airway microvasculature. Here, we show that HIF-1α mediates airway microvascular repair in a model of orthotopic tracheal transplantation. Grafts with a conditional knockout of Hif1a demonstrated diminished recruitment of recipient-derived Tie2⁺ angiogenic cells to the allograft, impaired repair of damaged microvasculature, accelerated loss of microvascular perfusion, and hastened denudation of epithelial cells. In contrast, graft HIF-1α overexpre2011-01-01T00:00:00Z2011 Jun2025-04-25T21:45:37.317Z2019-03-27T00:42:08ZS-EPMC31047702160659410.1172/JCI4619210.1172/jci46192