Control of oxygen homeostasis by hypoxia-inducible factor 1: Essential roles in embryogenesis, physiology, and disease pathogenesis

Hypoxia plays a clinically significant role in many different human diseases (reviewed in Ref. 1). Disorders associated with systemic hypoxia include altitude sickness, anemia, chronic obstructive pulmonary disease, congestive heart failure, congenital heart disease with right-to-left shunt, and high O2-affinity hemoglobinopathy. Vascular disorders are associated with local hypoxia, and in these diseases, O2 delivery, energy substrate delivery, and metabolite removal are all affected. Local hypoxia plays a significant role in the pathophysiology of cerebral, coronary, renal, and peripheral ischemic vascular disease. Hypoxia is also a major pathogenetic factor in other vascular-related disease processes, including retinal and tumor neovascularization.