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NCI: Hypoxia (or low O2 levels) affects various pathologies. First, tissue ischemia, a variation in O2 tension caused by hypoxia/reoxygenation, can lead to endothelial cell changes. For example, long periods of ischemia result in endothelial changes, such as vascular leakage, resulting in varicose veins. In more severe situations, ischemia can lead to myocardial or cerebral infarction and retinal vessel occlusion. Of interest, HIF-1 is stabilized prior to induction of vascular endothelial growth factor (VEGF) expression during acute ischemia in the human heart. Second, pulmonary hypertension associated with chronic respiratory disorders results from persistent vasoconstriction and vascular remodeling. Third, hypoxic gradients created in enlarging solid tumors trigger expression of genes containing hypoxia response elements (HREs) such as those involved in angiogenesis. This allows subsequent delivery of O2, nutrients, and further tumor growth. Vascular remodeling is an important component to tumorigenesis; wi
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