Mobilization of sca1/flk-1 positive endothelial progenitor cells declines in apolipoprotein E-deficient mice with a high-fat diet.
Mobilization of sca1/flk-1 positive endothelial progenitor cells declines in apolipoprotein E-deficient mice with a high-fat diet.
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DOI：
10.1016/j.jjcc.2015.02.008
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发表时间：
2015-12
影响因子：
2.5
通讯作者：
M. Steinmetz;Eva Lucanus;S. Zimmer;G. Nickenig;N. Werner
中科院分区：
文献类型：
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作者：
M. Steinmetz;Eva Lucanus;S. Zimmer;G. Nickenig;N. Werner
研究背景动脉粥样硬化的特征是各阶段内皮层的恶化。血管内皮细胞的修复与循环干细胞抗原1(SCA1)和血管内皮生长因子受体2(Flk-1)阳性内皮祖细胞(EPC)相关。方法和结果高脂饮食−/−小鼠外周血中内皮祖细胞减少，而骨髓中这些细胞的水平与对照组相比无明显变化。原位后肢灌流显示，与正常饮食的载脂蛋白E−/−小鼠相比，外周血中内皮祖细胞的动员减少，尽管血浆基质细胞衍生因子1α和反应性增加提示存在动员刺激。SCA1/Flk-1阳性细胞的增殖未见功能损伤，应用粒细胞集落刺激因子(GCSF)后，EPC不仅能从骨髓中显著动员，而且有耗竭骨髓库的趋势。正常饮食组和高脂血症组−/−小鼠血浆GCSF值相同，排除GCSF值下降。结论高脂血症−/−组小鼠骨髓细胞适应SCA1/Flk-1阳性EPC增殖和动员的能力可能过度紧张。
BackgroundAtherosclerosis features a deterioration of the endothelial layer in all stages. Restoration of the endothelium is associated with circulating stem cell antigen 1 (sca1) and vascular endothelial growth factor receptor type 2 (flk-1) positive endothelial progenitor cells (EPCs). We investigated whether EPC production and/or a mobilization from bone marrow are reduced in severe atherosclerosis.Methods and resultsEPCs in peripheral blood were diminished in ApoE−/− mice with high-fat diet (HFD) whereas bone marrow levels of these cells were not significantly altered compared to controls.In situ perfusion of the hind limbs demonstrated that EPC mobilization was reduced compared to ApoE−/− mice with normal chow, although increased plasma stromal cell-derived factor (SDF) 1α and responsivity suggested a mobilizing stimulus. The proliferation of sca1/flk-1 positive cells showed no functional impairment.EPCs could not only be significantly mobilized from the bone marrow through the application of granulocyte colony stimulating factor (GCSF), but also led by trend to a depletion of the bone marrow pool. GCSF levels in plasma were equal in ApoE−/− mice with normal chow or HFD, which excluded a decline in GCSF production.ConclusionThe capability of the bone marrow pool to adapt the proliferation and mobilization of sca1/flk-1 positive EPCs seems overstrained in ApoE−/− mice with a HFD.