Ruifrok Willem-Peter T, de Boer Rudolf A, Westenbrink B Daan, van Veldhuisen Dirk J, van Gilst Wiek H
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Eur J Pharmacol. 2008 May 13;585(2-3):270-7. doi: 10.1016/j.ejphar.2008.01.054. Epub 2008 Mar 15.
Erythropoietin is a haematopoietic hormone with extensive non-haematopoietic effects. The discovery of an erythropoietin receptor outside the haematopoietic system has fuelled the research into the beneficial effects of erythropoietin for various conditions, predominantly in cardiovascular disease. Experimental evidence has revealed the cytoprotective and angiogenic properties of erythropoietin and it seems that the erythropoietin-erythropoietin receptor system provides a powerful backbone against acute and chronic myocardial ischemia, each gaining from the different properties of erythropoietin. Clinical trials in which erythropoietin was titrated to achieve certain haematocrit levels have generated equivocal results. It has been suggested that a (too) high haematocrit is undesirable in cardiovascular disease. We have shown that intermittent (low-dose) erythropoietin administration, that does not increase haematocrit substantially, suffices to activate the beneficial downstream pathways of erythropoietin. We postulate that intermittent administration or a lower than conventional dose of erythropoietin, not only aimed at increasing haemoglobin at high levels, will provide powerful cellular protection and will improve cardiac outcome, without the side effects of erythropoietin associated with increased haematocrit.
促红细胞生成素是一种具有广泛非造血作用的造血激素。造血系统外促红细胞生成素受体的发现推动了对促红细胞生成素在各种病症中有益作用的研究，主要是在心血管疾病方面。实验证据揭示了促红细胞生成素的细胞保护和血管生成特性，而且促红细胞生成素 - 促红细胞生成素受体系统似乎为抵抗急性和慢性心肌缺血提供了强大支撑，二者均受益于促红细胞生成素的不同特性。将促红细胞生成素滴定至达到特定血细胞比容水平的临床试验产生了不确定的结果。有人提出，在心血管疾病中（过高的）血细胞比容是不可取的。我们已经表明，间歇性（低剂量）给予促红细胞生成素，虽不会大幅提高血细胞比容，但足以激活促红细胞生成素有益的下游途径。我们推测，间歇性给药或低于常规剂量的促红细胞生成素，不仅旨在高水平提高血红蛋白，还将提供强大的细胞保护并改善心脏预后，且不会产生与血细胞比容增加相关的促红细胞生成素副作用。
