Impaired physiological responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1α

摘要: Chronic hypoxia induces polycythemia, pulmonary hypertension, right ventricular hypertrophy, and weight loss. Hypoxia-inducible factor 1 (HIF-1) activates transcription of genes encoding proteins that mediate adaptive responses to hypoxia, including erythropoietin, vascular endothelial growth factor, glycolytic enzymes. Expression the HIF-1α subunit increases exponentially as O2 concentration is decreased. Hif1a–/– mouse embryos with complete deficiency due homozygosity for a null allele at Hif1a locus die midgestation, multiple cardiovascular malformations mesenchymal cell death. Hif1a+/– heterozygotes develop normally are indistinguishable from Hif1a+/+ wild-type littermates when maintained under normoxic conditions. In this study, physiological mice exposed 10% one six weeks were analyzed. demonstrated significantly delayed development remodeling greater loss compared littermates. These results indicate partial has significant effects on systemic chronic hypoxia. J. Clin. Invest. 103:691–696 (1999)