Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
PLoS One. 2012;7(5):e37934. doi: 10.1371/journal.pone.0037934. Epub 2012 May 24.
Bone marrow (BM)-derived stem/progenitor cells play an important role in ischemia-induced angiogenesis in cardiovascular diseases. Heat shock factor 1 (HSF1) is known to be induced in response to hypoxia and ischemia. We examined whether HSF1 contributes to ischemia-induced angiogenesis through the mobilization and recruitment of BM-derived stem/progenitor cells using HSF1-knockout (KO) mice. After the induction of ischemia, blood flow and microvessel density in the ischemic hindlimb were significantly lower in the HSF1-KO mice than in the wild-type (WT) mice. The mobilization of BM-derived Sca-1- and c-kit-positive cells in peripheral blood after ischemia was significantly lower in the HSF1-KO mice than in the WT mice. BM stem/progenitor cells from HSF1-KO mice showed a significant decrease in their recruitment to ischemic tissue and in migration, adhesion, and survival when compared with WT mice. Blood flow recovery in the ischemic hindlimb significantly decreased in WT mice receiving BM reconstitution with donor cells from HSF1-KO mice. Conversely, blood flow recovery in the ischemic hindlimb significantly increased in HSF1-KO mice receiving BM reconstitution with donor cells from WT mice. These findings suggest that HSF1 contributes to ischemia-induced angiogenesis by regulating the mobilization and recruitment of BM-derived stem/progenitor cells.
骨髓（BM）衍生的干细胞/祖细胞在心血管疾病中的缺血诱导血管生成中发挥重要作用。热休克因子 1（HSF1）已知可响应缺氧和缺血而被诱导。我们使用 HSF1 敲除（KO）小鼠检查 HSF1 是否通过动员和募集 BM 衍生的干细胞/祖细胞来促进缺血诱导的血管生成。在诱导缺血后，与野生型（WT）小鼠相比，HSF1-KO 小鼠缺血后肢的血流量和微血管密度明显降低。缺血后外周血中 BM 衍生的 Sca-1 和 c-kit 阳性细胞的动员在 HSF1-KO 小鼠中明显低于 WT 小鼠。与 WT 小鼠相比，HSF1-KO 小鼠的 BM 干细胞/祖细胞向缺血组织的募集以及迁移、黏附和存活能力明显下降。接受来自 HSF1-KO 小鼠供体细胞的 BM 再植入的 WT 小鼠的缺血后肢血流量恢复显著降低。相反，接受来自 WT 小鼠供体细胞的 BM 再植入的 HSF1-KO 小鼠的缺血后肢血流量恢复显著增加。这些发现表明 HSF1 通过调节 BM 衍生的干细胞/祖细胞的动员和募集来促进缺血诱导的血管生成。
