New strategy in treatment of diseases: hypoxia - inducible factor

Normal tissue function in mammals depends on adequate supply of oxygen. A discrepancy between oxygen supply and consumption (hypoxia) induces a variety of specific adaptation mechanisms. These mechanisms are in part governed by the activation of hypoxia inducible transcription factors (HIF-1, HIF-2, HIF-3). HIF-1ƒ is activated at physiologically relevant oxygen levels, ensuring fast and adequate response to hypoxia. HIF-1ƒ targets include genes involved in angiogenesis, vasomotor control, energy metabolism, apoptosis, innate immune defence. As a consequence of these various functions, HIF 1ƒ is also implicated in the pathophysiology of many human diseases. Delineation of HIF-hydroxylation pathways provides new targets for therapeutic intervention. There is increasing evidence that activation of HIF is protective in ischemic/hypoxic disease, Parkinson's disease and can generate a productive angiogenic response. A novel and essential role for HIF-1ƒ in regulation of several important polymorphonuclear leukocyte functions is described. At the same time, the inhibition of HIF 1 could provide new strategy for the treatment and prophylaxis of pulmonary hypertension and high-altitude edema as well as prevent alveolar epithelial cells from the destruction. Thus, the functions of HIF 1ƒ in the organism are polysemantic and demand further scrupulous investigations.