Deep venous thrombosis (DVT) is one of the most common peripheral vascular diseases. The roles of bone marrow-derived endothelial progenitor cells (EPCs) on the recanalization of venous thrombosis has been suggested recently, while the underlying mechanisms are not completely understood. Our objective was to investigate the functions of autophagy protein 5 (ATG5) in rat EPCs and its potential application in DVT. We have found that silencing of ATG5 or pharmacological suppression of ATG5 in rat EPCs reduces both the migration and psudotube formation under hypoxia in vitro. In line, overexpression of ATG5 significantly enhances the EPCs migration and psudotube formation capabilities. More importantly, injection of EPCs that stably express ATG5 increases EPC homing to the ischemic site and promotes thrombus recanalization in a rat DVT model in vivo. Mechanistically, we have shown that ATG5 overexpression enhances psudotube formation via the activation of AKT. These findings suggest that ATG5-AKT signaling plays an essential role in EPC migration and psudotube formation. Regulation of ATG5-AKT signaling may provide a potential novel therapy for DVT. (C) 2015 Published by Elsevier Ltd.
基金:
This work was supported by grants from National Natural
Science Foundation of China (No.81400345, NO.30972941),
Jiangsu Provincial Health Department’s Medical Science Program
(H201211), Science and Technology Innovation Program of
Suzhou Science Institution (SYS201234), Suzhou City’s Young
Scientific Talent Program (KJXW2013014), Graduate Research
and Innovation Program in Colleges and Universities of Jiangsu
Province (CXLX13_833), and Scientific Talent Program of the
Second Affiliated Hospital of Soochow University (SDFEYGJ1309).
第一作者机构:[1]Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China
共同第一作者:
通讯作者:
通讯机构:[*1]Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, No.1055, Sanxiang Road, Suzhou 215000, Jiangsu, China.
推荐引用方式(GB/T 7714):
Nan Hu,Ling-shang Kong,Hong Chen,et al.Autophagy protein 5 enhances the function of rat EPCs and promotes EPCs homing and thrombus recanalization via activating AKT[J].THROMBOSIS RESEARCH.2015,136(3):642-51.doi:10.1016/j.thromres.2015.06.038.
APA:
Nan Hu,Ling-shang Kong,Hong Chen,Wen-dong Li,Ai-min Qian...&Xiao-qiang Li.(2015).Autophagy protein 5 enhances the function of rat EPCs and promotes EPCs homing and thrombus recanalization via activating AKT.THROMBOSIS RESEARCH,136,(3)
MLA:
Nan Hu,et al."Autophagy protein 5 enhances the function of rat EPCs and promotes EPCs homing and thrombus recanalization via activating AKT".THROMBOSIS RESEARCH 136..3(2015):642-51