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有读书笔记有附件Statin and Stromal Cell-Derived Factor-1 Additively Promote Angiogenesis by Enhancement of Progenitor Cells Incorporation into New Vessels

cnefs 添加于 2011-9-7 23:39 | 1847 次阅读 | 0 个评论

  •  作 者

    Shao H, Tan Y, Eton D, Yang Z, Uberti MG, Li S, Schulick A, Yu H

  •  摘 要

    Angiogenesis requires the mobilization of progenitor cells from the bone marrow and homing of progenitor cells to ischemic tissue. Statins facilitate the former, and the chemokine stromal cell-derived factor-1 (SDF-1) enhances the latter. Their combined influence on angiogenesis was studied in vivo in the ischemic hindlimb C57BL/6 mouse model. The ischemic to non-ischemic perfusion ratio increased from 0.29 +/- 0.02 immediately after femoral excision to 0.51 +/- 0.10 three weeks after the surgery in the mice treated with either fluvastatin or SDF-1 alone, which is significantly better than the control (0.38 +/- 0.05, p < .05, n = 6). The combined use of fluvastatin and SDF-1 further improved the reperfusion ratio (0.62 +/- 0.08, p < .05). More cell proliferation, less apoptosis, enhanced bone marrow-derived endothelial progenitor cell (EPC) incorporation and higher capillary density were observed in ischemic tissue treated with both statin and SDF-1. In vitro mono-treatment with either fluvastatin (100 nM) or SDF-1 (100 ng/ml) facilitated EPC proliferation and migration, inhibited EPC apoptosis, enhanced expression of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9), and increased Akt phosphorylation and nitric oxide production. These effects were significantly augmented by the two agents together and ablated by inhibitors of either Akt or nitric oxide synthase (NOS). In conclusion, statin and SDF-1 additively enhance progenitor cell migration and proliferation and down-regulate EPC apoptosis, resulting in improved reperfusion via activation of the Akt/NOS pathway and up-regulation of MMP-2 and MMP-9 expression.

  •  详细资料

    • 文献种类:期刊
    • 期刊名称: Stem Cells
    • 期刊缩写: Stem Cells
    • 期卷页: 2008年  第26卷 第5期 1376-1384页
    • ISBN: 1066-5099

  •  所属群组

    分享干细胞研究   分享临床医学专题   分享cell  

  •  标 签

    血管新生  内皮祖细胞  缺血  SDF-1  他汀类 

  • 相关链接 DOI URL 

  •  附 件

    PDF附件原文 

  •  cnefs 的文献笔记  订阅

    他汀类药物与SDF-1共同促进祖细胞的血管新生作用
    他汀类药物可促进祖细胞从骨髓动员出来，而SDF-1可促进祖细胞进入缺血组织，进行血管再生。两者共同作用可以促进缺血组织的血管再生和康复。
    本研究以骨髓源性内皮祖细胞（EPC）为对象，研究他汀类药物和SDF-1对其的作用，以及给药后缺血组织的修复情况。
    体外实验发现单给他汀类药物或SDF-1可提高EPC的迁徙、增值、MMP-2和MMP-9、NO和Akt磷酸化，降低凋亡。并用抑制剂证明它们两者的作用是通过Akt/NOS途径对EPC起作用的。
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