Open AccessConcomitant overexpression of triple antioxidant enzymes selectively increases circulating endothelial progenitor cells in mice with limb ischaemia
Author(s) -
Liu Lingjuan,
Cui Yuqi,
Li Xin,
Que Xingyi,
Xiao Yuan,
Yang Chunlin,
Zhang Jia,
Xie Xiaoyun,
Cowan Peter J.,
Tian Jie,
Hao Hong,
Liu Zhenguo
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14287
Subject(s) - progenitor cell , endothelial progenitor cell , superoxide dismutase , cd34 , glutathione peroxidase , bone marrow , reactive oxygen species , peripheral blood mononuclear cell , apoptosis , biology , ischemia , population , immunology , endocrinology , andrology , oxidative stress , medicine , stem cell , microbiology and biotechnology , biochemistry , environmental health , in vitro
Endothelial progenitor cells (EPCs) are a group of heterogeneous cells in bone marrow (BM) and blood. Ischaemia increases reactive oxygen species (ROS) production that regulates EPC number and function. The present study was conducted to determine if ischaemia‐induced ROS differentially regulated individual EPC subpopulations using a mouse model concomitantly overexpressing superoxide dismutase (SOD)1, SOD3 and glutathione peroxidase. Limb ischaemia was induced by femoral artery ligation in male transgenic mice with their wild‐type littermate as control. BM and blood cells were collected for EPCs analysis and mononuclear cell intracellular ROS production, apoptosis and proliferation at baseline, day 3 and day 21 after ischaemia. Cells positive for c‐Kit + /CD31 + or Sca‐1 + /Flk‐1 + or CD34 + /CD133 + or CD34 + /Flk‐1 + were identified as EPCs. ischaemia significantly increased ROS production and cell apoptosis and decreased proliferation of circulating and BM mononuclear cells and increased BM and circulating EPCs levels. Overexpression of triple antioxidant enzymes effectively prevented ischaemia‐induced ROS production with significantly decreased cell apoptosis and preserved proliferation and significantly increased circulating EPCs level without significant changes in BM EPC populations, associated with enhanced recovery of blood flow and function of the ischemic limb. These data suggested that ischaemia‐induced ROS was differentially involved in the regulation of circulating EPC population.