Heat shock factor 1 contributes to ischemia-induced angiogenesis by regulating the mobilization and recruitment of bone marrow stem/progenitor cells.
Heat shock factor 1 contributes to ischemia-induced angiogenesis by regulating the mobilization and recruitment of bone marrow stem/progenitor cells.
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DOI：
10.1371/journal.pone.0037934
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Hamano K
中科院分区：
文献类型：
--
作者：
Kubo M;Li TS;Kurazumi H;Takemoto Y;Ohshima M;Yamamoto Y;Nishimoto A;Mikamo A;Fujimoto M;Nakai A;Hamano K
骨髓源性干/祖细胞在缺血诱导的心血管疾病血管新生中发挥重要作用。已知热休克因子1（HSF 1）响应于缺氧和缺血而被诱导。我们研究了HSF 1是否有助于缺血诱导的血管生成，通过动员和招募骨髓来源的干/祖细胞使用HSF 1基因敲除（KO）小鼠。在诱导缺血后，缺血后肢中的血流量和微血管密度在HSF 1-KO小鼠中显著低于野生型（WT）小鼠。缺血后外周血中BM来源的Sca-1和c-kit阳性细胞的动员在HSF 1-KO小鼠中显著低于WT小鼠。与WT小鼠相比，来自HSF 1-KO小鼠的BM干/祖细胞在向缺血组织的募集以及迁移、粘附和存活方面显示出显著降低。在接受来自HSF 1-KO小鼠的供体细胞的BM重建的WT小鼠中，缺血后肢中的血流恢复显著降低。相反，在接受来自WT小鼠的供体细胞的BM重建的HSF 1-KO小鼠中，缺血后肢中的血流恢复显著增加。这些发现表明，HSF 1有助于缺血诱导的血管生成，通过调节动员和招聘的BM衍生的干/祖细胞。
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.
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