期刊
STEM CELLS
卷 25, 期 2, 页码 297-304出版社
ALPHAMED PRESS
DOI: 10.1634/stemcells.2006-0340
关键词
oxidative stress; endothelial cells; stem cells; mitogen-activated protein kinase kinase kinase 5
资金
- NCI NIH HHS [1 K08 CA096579-01, P30 CA82709] Funding Source: Medline
- NHLBI NIH HHS [R01 HL077175-01] Funding Source: Medline
- NINDS NIH HHS [P50 NS052606] Funding Source: Medline
Endothelial progenitor cells (EPCs) circulate in the peripheral blood and reside in blood vessel walls. A hierarchy of EPCs exists where progenitors can be discriminated based on their clonogenic potential. EPCs are exposed to oxidative stress during vascular injury as residents of blood vessel walls or as circulating cells homing to sites of neovascularization. Given the links between oxidative injury, endothelial cell dysfunction, and vascular disease, we tested whether EPCs were sensitive to oxidative stress using newly developed clonogenic assays. Strikingly, in contrast to previous reports, we demonstrate that the most proliferative EPCs (high proliferative potential-endothelial colony-forming cells and low proliferative potential-endothelial colony-forming cells) had decreased clonogenic capacity after oxidant treatment. In addition, EPCs exhibited increased apoptosis and diminished tube-forming ability in vitro and in vivo in response to oxidative stress, which was directly linked to activation of a redox-dependent stress-induced kinase pathway. Thus, this study provides novel insights into the effect of oxidative stress on EPCs. Furthermore, this report outlines a framework for understanding how oxidative injury leads to vascular disease and potentially limits the efficacy of transplantation of EPCs into ischemic tissues enriched for reactive oxygen species and oxidized metabolites.
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