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Annu Rev Pathol. 2014;9:47-71. doi: 10.1146/annurev-pathol-012513-104720. Epub 2013 Aug 7.

Oxygen sensing, hypoxia-inducible factors, and disease pathophysiology.

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Vascular Program, Institute for Cell Engineering; Departments of Pediatrics, Medicine, Oncology, Radiation Oncology, and Biological Chemistry; and McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; email:


Hypoxia-inducible factors (HIFs) are transcriptional activators that function as master regulators of oxygen homeostasis, which is disrupted in disorders affecting the circulatory system and in cancer. The role of HIFs in these diseases has been elucidated by clinical studies and by analyses of mouse models. HIFs play a protective role in the pathophysiology of myocardial ischemia due to coronary artery disease, limb ischemia due to peripheral arterial disease, pressure-overload heart failure, wound healing, and chronic rejection of organ transplants. In contrast, HIFs contribute to the pathogenesis of pulmonary arterial hypertension, systemic hypertension associated with sleep apnea, ocular neovascularization, hereditary erythrocytosis, and cancer.

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