HIF prolyl hydroxylase inhibitors for anemia.

INTRODUCTION: The hypoxia-inducible factor (HIF) system mediates the body's response to hypoxia, locally, inducing angiogenesis and a shift to anaerobic metabolism, and systemically, increasing red cell mass in anemia. HIF prolyl hydroxylases (HIF-PH) modify HIF, decreasing its activity. Increasing HIF activity through inhibition of HIF-PH may provide an alternative treatment for anemia and may protect against damage related to ischemia-reperfusion. AREAS COVERED: The review discusses the basic science underpinnings of the HIF system and the clinical effects of the HIF system and its pharmacologic manipulation. EXPERT OPINION: Manipulation of the HIF system may improve outcomes in anemia by bypassing the effective iron deficiency found in anemia of chronic disease and by increasing red cell mass without supraphysiologic increases in erythropoietin. HIF-PH may also find a clinical use in the prevention of ischemia-reperfusion damage in strokes, cardiac ischemia, ischemic renal failure, etc.