Emergence of the Erythropoietin/Erythropoietin Receptor System as a Novel Cardiovascular Therapeutic Target
Emergence of the Erythropoietin/Erythropoietin Receptor System as a Novel Cardiovascular Therapeutic Target
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DOI：
10.1097/fjc.0b013e318235e7bb
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发表时间：
2011-12
影响因子：
3
通讯作者：
K. Satoh;Y. Fukumoto;M. Nakano;Y. Kagaya;H. Shimokawa
中科院分区：
文献类型：
--
作者：
K. Satoh;Y. Fukumoto;M. Nakano;Y. Kagaya;H. Shimokawa
摘要虽然已知缺氧和缺血与心血管疾病的发病机制有关，但具体的治疗靶点仍不清楚。为了解决这一重要问题，我们基于以下背景，针对促红细胞生成素(EPO)/EPO受体(EPOR)进行了两系列实验研究。长期以来，EPO一直被认为是一种造血激素，仅作用于红系祖细胞的增殖和分化。虽然最近的研究表明EPOR在心血管系统中表达，但EPOR/EPOR系统在体内的潜在保护作用仍有待研究。我们推测，血管EPO/EPOR系统对心血管疾病的发生具有重要的保护作用。利用血管EPOR缺陷小鼠，我们证明了血管EPO/EPOR系统对血管内皮功能和血管内环境的稳定起着至关重要的作用。在体内，血管EPO/EPOR系统对激活血管内皮生长因子/血管内皮生长因子受体-2系统、抑制缺氧性肺内皮损伤和促进缺血诱导的血管生成具有重要作用。这些结果表明，血管EPO/EPOR系统对缺氧/缺血具有重要的保护作用，表明该系统是心血管药物治疗的新靶点。
Abstract Although hypoxia and ischemia are known to be involved in the pathogenesis of cardiovascular disease, specific therapeutic targets still remain elusive. To address this important issue, we have performed 2 series of experimental studies, aiming at erythropoietin (Epo)/Epo receptor (EpoR) based on the following backgrounds. Epo has long been regarded as a hematopoietic hormone that acts exclusively in the proliferation and differentiation of erythroid progenitors. Although recent studies have demonstrated that EpoR is expressed in the cardiovascular system, the potential protective role of the vascular Epo/EpoR system in vivo remains to be examined. We hypothesized that the vascular Epo/EpoR system plays an important protective role against the development of cardiovascular disease. Using vascular EpoR-deficient mouse, we demonstrated that the vascular Epo/EpoR system plays a crucial role for endothelial function and vascular homeostasis. The vascular Epo/EpoR system is important for the activation of the vascular endothelial growth factor/vascular endothelial growth factor receptor-2 system, inhibits hypoxia-induced pulmonary endothelial damage and promotes ischemia-induced angiogenesis in vivo. These results indicate that the vascular Epo/EpoR system plays an important protective role against hypoxia/ischemia, demonstrating that this system is a novel therapeutic target in cardiovascular medicine.