Heat shock factor 1 contributes to ischemia-induced angiogenesis by regulating the mobilization and recruitment of bone marrow stem/progenitor cells.
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.
Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
Masayuki
M
Kubo
Tao-Sheng
TS
Li
Hiroshi
H
Kurazumi
Yoshihiro
Y
Takemoto
Mako
M
Ohshima
Yumi
Y
Yamamoto
Arata
A
Nishimoto
Akihito
A
Mikamo
Mitsuaki
M
Fujimoto
Akira
A
Nakai
Kimikazu
K
Hamano
D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D016026:Bone Marrow Transplantation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D006614:Hindlimb / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery; D007511:Ischemia / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D014157:Transcription Factors / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D043925:Angiogenesis Inducing Agents; D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A