PMID- 22744008
OWN - NLM
STAT- MEDLINE
DCOM- 20121123
LR  - 20200930
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Linking)
VI  - 303
IP  - 6
DP  - 2012 Sep 15
TI  - Fluid shear stress induces differentiation of circulating phenotype endothelial 
      progenitor cells.
PG  - C595-606
LID - 10.1152/ajpcell.00133.2012 [doi]
AB  - Endothelial progenitor cells (EPCs) are mobilized from bone marrow to peripheral 
      blood, and contribute to angiogenesis in tissue. In the process, EPCs are exposed 
      to shear stress generated by blood flow and tissue fluid flow. Our previous study 
      showed that shear stress induces differentiation of mature EPCs in adhesive 
      phenotype into mature endothelial cells and, moreover, arterial endothelial 
      cells. In this study we investigated whether immature EPCs in a circulating 
      phenotype differentiate into mature EPCs in response to shear stress. When 
      floating-circulating phenotype EPCs derived from ex vivo expanded human cord 
      blood were exposed to controlled levels of shear stress in a flow-loading device, 
      the bioactivities of adhesion, migration, proliferation, antiapoptosis, tube 
      formation, and differentiated type of EPC colony formation increased. The surface 
      protein expression rate of the endothelial markers VEGF receptor 1 (VEGF-R1) and 
      -2 (VEGF-R2), VE-cadherin, Tie2, VCAM1, integrin alpha(v)/beta(3), and E-selectin 
      increased in shear-stressed EPCs. The VEGF-R1, VEGF-R2, VE-cadherin, and Tie2 
      protein increases were dependent on the magnitude of shear stress. The mRNA 
      levels of VEGF-R1, VEGF-R2, VE-cadherin, Tie2, endothelial nitric oxide synthase, 
      matrix metalloproteinase 9, and VEGF increased in shear-stressed EPCs. Inhibitor 
      analysis showed that the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of 
      rapamycin (mTOR) signal transduction pathway is a potent activator of adhesion, 
      proliferation, tube formation, and differentiation in response to shear stress. 
      Western blot analysis revealed that shear stress activated the VEGF-R2 
      phosphorylation in a ligand-independent manner. These results indicate that shear 
      stress increases differentiation, adhesion, migration, proliferation, 
      antiapoptosis, and vasculogenesis of circulating phenotype EPCs by activation of 
      VEGF-R2 and the PI3K/Akt/mTOR signal transduction pathway.
FAU - Obi, Syotaro
AU  - Obi S
AD  - Department of Regenerative Medicine Science, Tokai University School of Medicine, 
      Isehara, Japan.
FAU - Masuda, Haruchika
AU  - Masuda H
FAU - Shizuno, Tomoko
AU  - Shizuno T
FAU - Sato, Atsuko
AU  - Sato A
FAU - Yamamoto, Kimiko
AU  - Yamamoto K
FAU - Ando, Joji
AU  - Ando J
FAU - Abe, Yusuke
AU  - Abe Y
FAU - Asahara, Takayuki
AU  - Asahara T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120627
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
SB  - IM
MH  - Cell Adhesion/physiology
MH  - Cell Differentiation/*physiology
MH  - Cell Movement/physiology
MH  - Cells, Cultured
MH  - Endothelial Cells/*physiology
MH  - Endothelium, Vascular/cytology/*physiology
MH  - Fetal Blood/physiology
MH  - Humans
MH  - Membrane Fluidity/physiology
MH  - *Phenotype
MH  - *Shear Strength
MH  - Stem Cells/*physiology
MH  - *Stress, Mechanical
EDAT- 2012/06/30 06:00
MHDA- 2012/12/10 06:00
CRDT- 2012/06/30 06:00
PHST- 2012/06/30 06:00 [entrez]
PHST- 2012/06/30 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
AID - ajpcell.00133.2012 [pii]
AID - 10.1152/ajpcell.00133.2012 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2012 Sep 15;303(6):C595-606. doi: 
      10.1152/ajpcell.00133.2012. Epub 2012 Jun 27.