Shear stress and vascular smooth muscle cells promote endothelial differentiation of endothelial progenitor cells via activation of Akt.
BACKGROUND
The structural and functional integrity of endothelium plays a pivotal role in the pathogenesis of cardiovascular diseases. Endothelial progenitor cells (EPCs) is a population of pluripotent cells, which have a crucial role in maintaining the integrity of endothelium, but the mechanisms regulating the differentiation of EPCs have not been understood completely. In this study, the effects of shear stress and vascular smooth muscle cells (VSMCs) on the differentiation of EPCs, as well as the role of Akt were examined in a coculture model.


METHODS
Human EPCs separated from cord blood were subjected to shear stress by using a parallel-plate coculture flow chamber. The expression of CD133, CD34, CD31 and von Willebrand factor of EPCs were assessed by a flow cytometry. Activation of Akt was detected by Western blot.


RESULTS
Both shear stress and VSMCs increase the expression of endothelial markers, CD31 and von Willebrand factor (vWF), simultaneously, decrease progenitor markers, CD133 and CD34, of EPCs. However, the effect of shear stress on EPC differentiation was much more significant when VMSCs were presented. Akt was activated in EPCs by shear stress, VSMCs or both. When the activation of Akt was blocked with its inhibitor during EPCs exposed to shear stress, CD133 and CD34 expressions were upregulated and correspondingly CD31 and vWF expressions were downregulated significantly.


CONCLUSIONS
The results demonstrate that shear stress and VSMCs promote endothelial differentiation of EPCs via activation of Akt, which provide a new insight to clinical application on the regeneration of the vascular endothelium.
Ye
Cao
C
Institute of Mechanobiology and Medical Engineering, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
Bai
Ling
L
Yan
Zhi-Qiang
ZQ
Wang
Yan-Hua
YH
Jiang
Zong-Lai
ZL
D002454:Cell Differentiation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D033081:Shear Strength; D013314:Stress, Mechanical
D051057:Proto-Oncogene Proteins c-akt