Abstract 15171: Heat Shock Transcription Factor 1 Contributes to Ischemia-induced Angiogenesis by Regulating Kinetics of Bone Marrow Stem Cells
Background: Recent evidence suggests bone marrow (BM)-derived stem cells contribute to ischemia-induced angiogenesis in the cardiovascular diseases. Heat shock transcription factor 1 (HSF1) is known to be induced in response to stress including hypoxia and ischemia. Therefore, we assessed the hypothesis that HSF1 contributes to angiogenesis through the mobilization and recruitment of BM-derived stem cells, in response to ischemia.
Methods and Results: We used wild type (WT) and HSF1-knockout (KO) mice of ICR background. Three weeks after the induction of ischemia, blood flow and microvessel density in the ischemic hindlimb were significantly worse in the HSF1-KO mice than in the WT mice (P<0.001). The mobilization of BM-derived Sca-1 positive cells in peripheral blood were significantly less in the HSF1-KO mice than in the WT mice, 3 days after ischemia (P<0.01). BM stem cells from HSF1-KO mice showed a significant decrease in the in vitro cell migration (P<0.05) and in vivo recruitment into the ischemic tissue (P<0.01) when compared with those from WT mice. The recovery of blood flow in the ischemic hindlimb was significantly decreased in WT mice receiving BM reconstitution with donor cells from HSF1-KO mice (P<0.001, Figure). Conversely, the blood flow in the ischemic hindlimb was significantly improved in recipient HSF1-KO mice receiving BM reconstitution with donor cells from WT mice (P<0.01, Figure).
Conclusion: HSF1 plays a key role in ischemia-induced angiogenesis by regulating the kinetics of BM-derived stem cells.
- © 2010 by American Heart Association, Inc.