Granulocyte colony-stimulating factor and granulocyte macrophage colony-stimulating factor exacerbate atherosclerosis in apolipoprotein E-deficient mice
Granulocyte colony-stimulating factor and granulocyte macrophage colony-stimulating factor exacerbate atherosclerosis in apolipoprotein E-deficient mice
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DOI：
10.1161/circulationaha.106.665570
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发表时间：
2007-04-17
期刊：
影响因子：
37.8
通讯作者：
Taylor, W. Robert
中科院分区：
文献类型：
--
作者：
Haghighat, Amir;Weiss, Daiana;Taylor, W. Robert
最近的研究表明，骨髓来源的祖细胞对血管修复有潜在的贡献。初步临床研究探讨了粒细胞巨噬细胞集落刺激因子（GM-CSF）和粒细胞集落刺激因子（G-CSF）动员祖细胞影响血管修复的可能性。然而，目前尚不清楚短期给药G-CSF或GM-CSF是否对动脉粥样硬化有有益作用。方法与结果：以10 μ g剂量的GM-CSF或g - csf分别治疗载脂蛋白e缺陷小鼠。公斤(1)。d(-1) SC每天给药，每周交替给药5天，共20次，为期8周。我们发现，在维持高脂肪饮食的动物中，G-CSF和GM-CSF实际上都表现出动脉粥样硬化病变程度的增加。动脉粥样硬化程度的增加与炎症细胞或促炎基因表达的增加无关。有趣的是，血管外血管明显增加，提示血管血管新生的机制作用。结论-这些发现表明，在动脉粥样硬化动物模型中，G-CSF或GM-CSF不仅没有显示出任何有益的治疗效果，而且两者都导致动脉粥样硬化的恶化。
Background-Recent studies have suggested a potential contribution of bone marrow-derived progenitor cells to vascular repair. Preliminary clinical studies have explored the possibility that mobilization of progenitor cells with granulocyte macrophage colony-stimulating factor ( GM-CSF) and granulocyte colony-stimulating factor ( G-CSF) can affect vascular repair. However, it is not known whether the short-term administration of G-CSF or GM-CSF exerts beneficial effects on atherosclerosis.Methods and Results-Apolipoprotein E-deficient mice were treated with either GM-CSF or G-CSF at a dose of 10 mu g . kg(-1) . d(-1) SC administered daily for 5 days per week on alternating weeks for a total of 20 doses over an 8-week treatment period. We found that in animals maintained on a high-fat diet, both G-CSF and GM-CSF actually demonstrated an increase in atherosclerotic lesion extent. The increase in atherosclerotic extent was not associated with an increase in either inflammatory cells or expression of proinflammatory genes. Interestingly, adventitial vascularity significantly increased, suggesting a mechanistic role for vasa vasorum neovascularization.Conclusions-These findings demonstrate that in this animal model of atherosclerosis, not only did administration of G-CSF or GM-CSF fail to demonstrate any beneficial therapeutic effect, but both resulted in a worsening of atherosclerosis.