Stem cell factor receptor induces progenitor and natural killer cell-mediated cardiac survival and repair after myocardial infarction

• Bilal B. Ayach

  *Toronto General Hospital Research Institute and

• Makoto Yoshimitsu

  Ontario Cancer Institute, University Health Network, Toronto, ON, Canada M5G 2C4; and

• Fayez Dawood

  *Toronto General Hospital Research Institute and

• Mei Sun

  *Toronto General Hospital Research Institute and

• Sara Arab

  *Toronto General Hospital Research Institute and

• Manyin Chen

  *Toronto General Hospital Research Institute and

• Koji Higuchi

  Ontario Cancer Institute, University Health Network, Toronto, ON, Canada M5G 2C4; and

• Christopher Siatskas

  Ontario Cancer Institute, University Health Network, Toronto, ON, Canada M5G 2C4; and

• Paul Lee

  *Toronto General Hospital Research Institute and

• Hilda Lim

  *Toronto General Hospital Research Institute and

• Jane Zhang

  *Toronto General Hospital Research Institute and

• Eva Cukerman

  *Toronto General Hospital Research Institute and

• William L. Stanford

  Institute of Biomaterials and Biomedical Engineering and

• Jeffrey A. Medin

  Ontario Cancer Institute, University Health Network, Toronto, ON, Canada M5G 2C4; and

• Peter P. Liu

  *Toronto General Hospital Research Institute and

抄録

Inappropriate cardiac remodeling and repair after myocardial infarction (MI) predisposes to heart failure. Studies have reported on the potential for lineage negative, steel factor positive ( c - kit + ) bone marrow-derived hematopoetic stem∕progenitor cells (HSPCs) to repair damaged myocardium through neovascularization and myogenesis. However, the precise contribution of the c-kit signaling pathway to the cardiac repair process has yet to be determined. In this study, we sought to directly elucidate the mechanistic contributions of c-kit + bone marrow-derived hematopoetic stem∕progenitor cells in the maintenance and repair of damaged myocardium after MI. Using c-kit -deficient mice, we demonstrate the importance of c-kit signaling in preventing ventricular dilation and hypertrophy, and the maintenance of cardiac function after MI in c-kit -deficient mice. Furthermore, we show phenotypic rescue of cardiac repair after MI of c-kit -deficient mice by bone marrow transplantation of wild-type HSPCs. The transplanted group also had reduced apoptosis and collagen deposition, along with an increase in neovascularization. To better understand the mechanisms underlying this phenotypic rescue, we investigated the gene expression pattern within the infarcted region by using microarray analysis. This analysis suggested activation of inflammatory pathways, specifically natural killer (NK) cell-mediated mobilization after MI in rescued hearts. This finding was confirmed by immunohistology and by using an NK blocker. Thus, our investigation revealed a previously uncharacterized role for c-kit signaling after infarction by mediating bone marrow-derived NK and angiogenic cell mobilization, which contributes to improved remodeling and cardiac function after MI.

収録刊行物

• Proceedings of the National Academy of Sciences

  Proceedings of the National Academy of Sciences 103 (7), 2304-2309, 2006-02-07

  Proceedings of the National Academy of Sciences

キーワード

• Multidisciplinary

詳細情報

• CRID: 1360298763135720192
• NII論文ID: 30016243509
• DOI: 10.1073/pnas.0510997103
• ISSN: 10916490
• ISSN: 00278424
• Web Site: https://pnas.org/doi/pdf/10.1073/pnas.0510997103
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