New Jersey Medical School, Newark, 07103, USA.
Expert Opin Investig Drugs. 2011 May;20(5):645-56. doi: 10.1517/13543784.2011.566861. Epub 2011 Mar 16.
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.
The review discusses the basic science underpinnings of the HIF system and the clinical effects of the HIF system and its pharmacologic manipulation.
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.
缺氧诱导因子 (HIF) 系统介导了机体对缺氧的反应，在局部诱导血管生成和无氧代谢转变，在全身增加贫血患者的红细胞量。HIF 脯氨酰羟化酶（HIF-PH）修饰 HIF，降低其活性。通过抑制 HIF-PH 增加 HIF 活性可能为贫血的治疗提供一种替代方法，并可能预防与缺血再灌注相关的损伤。
本综述讨论了 HIF 系统的基础科学基础及其在临床中的作用以及对其的药理学操作。
通过绕过慢性病性贫血中存在的有效铁缺乏，以及在不引起红细胞生成素超生理增加的情况下增加红细胞量，对 HIF 系统的操作可能改善贫血的预后。HIF-PH 也可能在预防中风、心肌缺血、缺血性肾衰竭等的缺血再灌注损伤方面找到临床应用。
