Impaired Vps34 complex activity-mediated autophagy inhibition contributes to endothelial progenitor cells damage in the ischemic conditions.
AIMS
Endothelial progenitor cells (EPCs) are widely accepted to be applied in ischemic diseases. However, the therapeutic potency is largely impeded because of its inviability in these ischemic conditions. Autophagy is recognized to be vital in cell activity. Therefore, we explore the role and the mechanism of autophagy in ischemic EPCs.


METHODS AND RESULTS
We applied 7d-cultured bone marrow EPCs to investigate the autophagy status under the oxygen and glucose deprivation (OGD) conditions in vitro, mimicking the in-vivo harsh ischemia and anoxia microenvironment. We found increased EPC apoptosis, accompanied by an impaired autophagy activation. Intriguingly, mTOR inhibitor Rapamycin was incapable to reverse this damped autophagy and EPC damage. We further found that autophagy pathway downstream Vps34-Beclin1-Atg14 complex assembly and activity were impaired in OGD conditions, and an autophagy-inducing peptide Tat-Beclin1 largely recovered the impaired complex activity and attenuated OGD-stimulated EPC injury through restoring autophagy activation.


CONCLUSIONS
The present study discovered that autophagy activation is inhibited when EPCs located in the ischemia and anoxia conditions. Restoration of Vps34 complex activity obtains sufficient autophagy, thus promoting EPC survival, which will provide a potential target and advance our understanding of autophagy manipulation in stem cell transplantation.
['Jiang|Ru-Chao|RC|', 'Zhang|Xiao-Ling|XL|', 'Zhang|Qi-Ai|QA|', 'Zheng|Xue-Ying|XY|', 'Shi|Hai-Jie|HJ|', 'Qin|Yuan|Y|', 'Zhang|Gui-Ping|GP|', 'Xiao|Qing|Q|', 'Luo|Jian-Dong|JD|']
D000818:Animals D017209:Apoptosis D001343:Autophagy D000071186:Beclin-1 D058546:Class III Phosphatidylinositol 3-Kinases D066026:Endothelial Progenitor Cells D005947:Glucose D007511:Ischemia D008297:Male D008810:Mice, Inbred C57BL D010100:Oxygen D020123:Sirolimus D054322:tat Gene Products, Human Immunodeficiency Virus
Vps34 complex Autophagy Endothelial progenitor cells Ischemia conditions