1. Endothelial progenitor cells attenuate the lung ischemia/reperfusion injury following lung transplantation via the endothelial nitric oxide synthase pathway.
- Author
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Gao, Wei, Jiang, Tao, Liu, Yan-hong, Ding, Wen-gang, Guo, Chang-chun, and Cui, Xiao-guang
- Abstract
Abstract Objective Endothelial progenitor cells (EPCs) can improve endothelial integrity. This study aimed to examine the effects and the mechanism of EPCs on lung ischemia-reperfusion injury (LIRI). Methods Wistar rats were randomized into the sham or the left lung transplantation group. The recipients were randomized and treated with vehicle as the LIRI group, with EPC as the EPC group, or with N5-(1-iminoethyl)-l-ornithine-pretreated EPC as the EPC/L group (n = 8 per group). The ratios of arterial oxygen partial pressure to fractional inspiratory oxygen were measured. The lung wet-to-dry weight ratios, protein levels, and injury, as well as the levels of plasma cytokines, were examined. The levels of endothelin (ET)-1, endothelial nitric oxide synthase (eNOS), phosphorylated eNOS, inducible NOS, phosphorylated myosin light chain, nuclear factor-κBp65, Bax, Bcl-2, cleaved caspase-3, and myeloperoxidase in the graft lungs were detected. Results Compared with the LIRI group, EPC treatment significantly increased the ratios of arterial oxygen partial pressure to fractional inspiratory oxygen and decreased the lung wet-to-dry weight ratios and protein levels in the grafts, accompanied by increasing eNOS expression and phosphorylation, but decreasing endothelin-1, inducible NOS, phosphorylated nuclear factor-kBp65, phosphorylated myosin light chain expression, and myeloperoxidase activity. EPCs reduced lung tissue damage and apoptosis associated with decreased levels of Bax and cleaved caspase-3 expression, but increased Bcl-2 expression. EPC treatment significantly reduced the levels of serum proinflammatory factors, but elevated levels of interleukin-10. In contrast, the protective effect of EPCs were mitigated and abrogated by N5-(1-iminoethyl)-l-ornithine pretreatment. Conclusions Data indicated that EPC ameliorated LIRI by increasing eNOS expression. Graphical abstract [ABSTRACT FROM AUTHOR]
- Published
- 2019
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