Erythropoietin stimulates normal endothelial progenitor cell-mediated endothelial turnover, but attributes to neovascularization only in the presence of local ischemia

被引：47

作者：

Westenbrink, B. Daan ^{[1
]}

Oeseburg, Hisko ^{[1
]}

Kleijn, Lennaert ^{[1
]}

van der Harst, Pim ^{[1
]}

Belonje, Anne M. S. ^{[1
]}

Voors, Adriaan A. ^{[1
]}

Schoemaker, Regien G. ^{[1
]}

De Boer, Rudolf A. ^{[1
]}

van Veldhuisen, Dirk J. ^{[1
]}

van Gilst, Wiek H. ^{[1
]}

机构：

[1] Univ Groningen, Univ Med Ctr Groningen, Thoraxctr, Dept Cardiol, NL-9700 RB Groningen, Netherlands

来源：

CARDIOVASCULAR DRUGS AND THERAPY | 2008年 / 22卷 / 04期

关键词：

erythropoietin; endothelial function; heart failure; endothelial progenitor cells;

D O I：

10.1007/s10557-008-6094-y

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Purpose We aimed to evaluate whether ischemia is required for erythropoietin (EPO) induced stimulation of endothelial progenitor cells (EPCs) and their related effects on endothelial and cardiac function. Methods Bone marrow of rats was replaced by transgenic cells to allow tracking of EPCs. Ischemic heart failure was induced by left coronary artery ligation to induce myocardial infarction (MI) and control rats received a sham procedure. Three weeks after surgery, rats were randomized to receive EPO (darbepoetin alfa 40 mu g/kg per 3 weeks) or vehicle and were sacrificed 9 weeks after surgery. Results In all treated groups, EPO significantly increased circulating EPCs and their incorporation into the endothelium of the ischemic and non-ischemic hearts as well as in the control organs; kidney and liver. This was associated with significantly improved endothelial function, which was strongly correlated with circulating EPCs (R=0.7, p<0.01). However, additional EPCs preferentially homed to the ischemic MI borderzone ( p<0.01) resulting in specific EPO-induced improvement of cardiac microvascularization and performance only in ischemic hearts (all p<0.05). The differential stimulation of neovascularization by EPO was associated with increased EPO-receptor and VEGF expression in ischemic hearts only. Conclusions In general, EPO stimulates normal endothelial progenitor cell-mediated endothelial turnover, but improves cardiac microvascularization and function only in the presence of ischemia.

引用

页码：265 / 274

页数：10

共 36 条

[1] Low-dose therapy with the long-acting erythropoietin analogue darbepoetin alpha persistently activates endothelial Akt and attenuates progressive organ failure [J].