Steinmetz Martin, Lucanus Eva, Zimmer Sebastian, Nickenig Georg, Werner Nikos
Medizinische Klinik und Poliklinik II, Kardiologie/Angiologie/Pulmologie/Internistische Intensivmedizin, Universitätsklinikum Bonn, Bonn, Germany; Institut National de la Santé et de la Recherche Médicale (INSERM), Unit 970, Paris Cardiovascular Research Center, Paris, France.
Medizinische Klinik und Poliklinik II, Kardiologie/Angiologie/Pulmologie/Internistische Intensivmedizin, Universitätsklinikum Bonn, Bonn, Germany.
J Cardiol. 2015 Dec;66(6):532-8. doi: 10.1016/j.jjcc.2015.02.008. Epub 2015 Mar 24.
Atherosclerosis 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.
EPCs 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.
The 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.
动脉粥样硬化在各个阶段均以内皮细胞层恶化为特征。内皮细胞的恢复与循环中的干细胞抗原1（Sca1）和血管内皮生长因子受体2（Flk-1）阳性的内皮祖细胞（EPC）有关。我们研究了在严重动脉粥样硬化中EPC的产生和/或从骨髓中的动员是否减少。
高脂饮食（HFD）的ApoE-/-小鼠外周血中的EPC减少，而与对照组相比，这些细胞的骨髓水平没有明显改变。后肢原位灌注显示，与正常饮食的ApoE-/-小鼠相比，EPC的动员减少，尽管血浆基质细胞衍生因子（SDF）1α增加和反应性提示有动员刺激。Sca1/Flk-1阳性细胞的增殖未显示功能受损。EPC不仅可以通过应用粒细胞集落刺激因子（GCSF）从骨髓中显著动员出来，而且在趋势上还导致骨髓池的消耗。正常饮食或HFD的ApoE-/-小鼠血浆中的GCSF水平相等，这排除了GCSF产生的下降。
在高脂饮食的ApoE-/-小鼠中，骨髓池适应Sca1/Flk-1阳性EPC增殖和动员的能力似乎过度紧张。
