51. Reverse-D-4F improves endothelial progenitor cell function and attenuates LPS-induced acute lung injury
- Author
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Nana Yang, Hua Tian, Enxin Zhan, Lei Zhai, Peng Jiao, Shutong Yao, Guohua Lu, Qingjie Mu, Juan Wang, Aihua Zhao, Yadong Zhou, and Shucun Qin
- Subjects
Acute lung injury ,Endothelial progenitor cells ,Reverse D-4F ,Apolipoprotein A-I ,Endothelial nitric oxide synthase ,Diseases of the respiratory system ,RC705-779 - Abstract
Abstract Background Patients with acute lung injury (ALI) have increased levels of pro-inflammatory mediators, which impair endothelial progenitor cell (EPC) function. Increasing the number of EPC and alleviating EPC dysfunction induced by pro-inflammatory mediators play important roles in suppressing ALI development. Because the high density lipoprotein reverse-D-4F (Rev-D4F) improves EPC function, we hypothesized that it might repair lipopolysaccharide (LPS)-induced lung damage by improving EPC numbers and function in an LPS-induced ALI mouse model. Methods LPS was used to induce ALI in mice, and then the mice received intraperitoneal injections of Rev-D4F. Immunohistochemical staining, flow cytometry, MTT, transwell, and western blotting were used to assess the effect of Rev-D4F on repairment of lung impairment, and improvement of EPC numbers and function, as well as the signaling pathways involved. Results Rev-D4F inhibits LPS-induced pulmonary edema and decreases plasma levels of the pro-inflammatory mediators TNF-α and ET-1 in ALI mice. Rev-D4F inhibited infiltration of red and white blood cells into the interstitial space, reduced lung injury-induced inflammation, and restored injured pulmonary capillary endothelial cells. In addition, Rev-D4F increased numbers of circulating EPC, stimulated EPC differentiation, and improved EPC function impaired by LPS. Rev-D4F also acted via a PI3-kinase-dependent mechanism to restore levels of phospho-AKT, eNOS, and phospho-eNOS suppressed by LPS. Conclusions These findings indicate that Rev-D4F has an important vasculoprotective role in ALI by improving the EPC numbers and functions, and Rev-D4F reverses LPS-induced EPC dysfuncion partially through PI3K/AKT/eNOS signaling pathway.
- Published
- 2019
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