scholarly journals Maturing EPCs into endothelial cells: may the force be with the EPCs. Focus on “Fluid shear stress induces differentiation of circulating phenotype endothelial progenitor cells”

2012 ◽  
Vol 303 (6) ◽  
pp. C589-C591 ◽  
Author(s):  
Randall F. Ankeny ◽  
Casey J. Ankeny ◽  
Robert M. Nerem ◽  
Hanjoong Jo
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Fluid Shear Stress ◽  
Fluid Shear ◽  
Endothelial Progenitor

Shear stress regulates inflammatory and thrombogenic gene transcripts in cultured human endothelial progenitor cells

2010 ◽  
Vol 104 (09) ◽  
pp. 582-591 ◽  
Author(s):  
Trine Lund ◽  
Stig Hermansen ◽  
Thomas Andreasen ◽  
Jan Olsen ◽  
Bjarne Østerud ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Mrna Expression ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Mrna Levels ◽  
Endothelial Progenitor ◽  
Gene Transcripts ◽  
Nos Inhibitor

SummaryShear stress has an established effect on mature endothelial cells, but less is known about how shear stress regulates endothelial progenitor cells (EPCs). In vitro expanded EPCs isolated from adult human blood represent a novel tool in regenerative vessel therapy. However, in vitro culturing may generate cells with unfavourable properties. The aim of the present study was therefore to assess whether shear stress may influence the inflammatory and thrombotic phenotype of in vitro expanded EPCs. In late outgrowth EPCs, 6 hours of shear stress (6.0 dynes/ cm2) significantly reduced the mRNA levels of IL-8, COX2, and tissue factor (TF) compared to static controls. This was associated with a reduced TF activity. In contrast, mRNA expression of NOS3 was significantly increased following 6 and 24 hours of shear stress. In accordance with this, NOS3 protein expression was increased following 24 hours of shear stress. Overall stimulation with the proinflammatory mediator, TNFα, for the final 2 hours increased the mRNA expression of IL-6, IL-8, MCP-1, ICAM1, and TF. However exposure to 6 hours of shear stress significantly suppressed the inductory potential of TNFα to increase the mRNA levels of IL-6, IL-8, COX2, and TF. Additionally, TNFα increased TF activity approximately 10 times, an effect that was also significantly reduced by exposure to 6 and 24 hours of shear stress. The effect of shear on the gene levels of TF and NOS3 were not blocked by the NOS inhibitor L-NAME. These observations suggest that EPCs are capable of functionally responding to shear stress.

Fluid shear stress induces arterial differentiation of endothelial progenitor cells

2009 ◽  
Vol 106 (1) ◽  
pp. 203-211 ◽  
Author(s):  
Syotaro Obi ◽  
Kimiko Yamamoto ◽  
Nobutaka Shimizu ◽  
Shinichiro Kumagaya ◽  
Tomomi Masumura ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Peripheral Blood ◽  
Consensus Sequence ◽  
Mrna Levels ◽  
Endothelial Progenitor ◽  
Cell Markers

Endothelial progenitor cells (EPCs) are mobilized from bone marrow to peripheral blood and contribute to angiogenesis in tissues. In the process, EPCs are exposed to the shear stress generated by blood flow and tissue fluid flow. Our previous study showed that shear stress promotes differentiation of EPCs into mature endothelial cells. In this study, we investigated whether EPCs differentiate into arterial or venous endothelial cells in response to shear stress. When cultured EPCs derived from human peripheral blood were exposed to controlled levels of shear stress in a flow-loading device, the mRNA levels of the arterial endothelial cell markers ephrinB2, Notch1/3, Hey1/2, and activin receptor-like kinase 1 increased, but the mRNA levels of the venous endothelial cell markers EphB4 and neuropilin-2 decreased. Both the ephrinB2 increase and the EphB4 decrease were shear stress dependent rather than shear rate dependent. EphrinB2 protein was increased in shear-stressed EPCs, and the increase in ephrinB2 expression was due to activated transcription and not mRNA stabilization. Deletion analysis of the ephrinB2 promoter indicated that the cis-element (shear stress response element) is present within 106 bp 5′ upstream from the transcription initiation site. This region contains the Sp1 consensus sequence, and a mutation in its sequence decreased the basal level of transcription and abolished shear stress-induced ephrinB2 transcription. Electrophoretic mobility shift assays and chromatin immunoprecipitation assays showed that shear stress markedly increased binding of Sp1 to its consensus sequence. These results indicate that shear stress induces differentiation of EPCs into arterial endothelial cells by increasing ephrinB2 expression in EPCs through Sp1 activation.

Fluid shear stress induces differentiation of circulating phenotype endothelial progenitor cells

2012 ◽  
Vol 303 (6) ◽  
pp. C595-C606 ◽  
Author(s):  
Syotaro Obi ◽  
Haruchika Masuda ◽  
Tomoko Shizuno ◽  
Atsuko Sato ◽  
Kimiko Yamamoto ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Signal Transduction Pathway ◽  
Tube Formation ◽  
Tissue Fluid ◽  
Transduction Pathway ◽  
Endothelial Progenitor

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 αv/β3, 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.

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