Shear stress and interleukin-8 (IL-8) on the proliferation, differentiation and tube formation of endothelial progenitor cells (EPCs)

2011 ◽  
Vol 10 (83) ◽  
Author(s):  
Zhou Shu
Keyword(s):  
Shear Stress ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Tube Formation ◽  
Interleukin 8 ◽  
Endothelial Progenitor

Proliferation, differentiation, and tube formation by endothelial progenitor cells in response to shear stress

2003 ◽  
Vol 95 (5) ◽  
pp. 2081-2088 ◽  
Author(s):  
Kimiko Yamamoto ◽  
Tomono Takahashi ◽  
Takayuki Asahara ◽  
Norihiko Ohura ◽  
Takaaki Sokabe ◽  
...  
Keyword(s):  
Shear Stress ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Peripheral Blood ◽  
Tube Formation ◽  
Target Tissue ◽  
Tissue Fluid ◽  
Vascular Endothelial ◽  
Endothelial Progenitor ◽  
Static Conditions

Endothelial progenitor cells (EPCs), circulating in peripheral blood, migrate toward target tissue, differentiate, and contribute to the formation of new vessels. In this study, we report that shear stress generated by blood flow or tissue fluid flow can accelerate the proliferation, differentiation, and capillary-like tube formation of EPCs. When EPCs cultured from human peripheral blood were subjected to laminar shear stress, the cells elongated and oriented their long axes in the direction of flow. The cell density of the EPCs exposed to shear stress was higher, and a larger percentage of these cells were in the G2-M phase of the cell cycle, compared with EPCs cultured under static conditions. Shear stress markedly increased the EPC expression of two vascular endothelial growth factor receptors, kinase insert domain-containing receptor and fms-like tyrosine kinase-1, and an intercellular adhesion molecule, vascular endothelial-cadherin, at both the protein and mRNA levels. Assays for tube formation in the collagen gels showed that the shear-stressed EPCs formed tubelike structures and developed an extensive tubular network significantly faster than the static controls. These findings suggest that EPCs are sensitive to shear stress and that their vasculogenic activities may be modulated by shear stress.

scholarly journals Shear Stress Triggers Angiogenesis of Late Endothelial Progenitor Cells via the PTEN/Akt/GTPCH/BH4 Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Shao-Hong Wu ◽  
Feng Zhang ◽  
Shun Yao ◽  
Lu Tang ◽  
Hai-Tao Zeng ◽  
...  
Keyword(s):  
Shear Stress ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Limb Ischemia ◽  
Tube Formation ◽  
Laminar Shear Stress ◽  
Endothelial Progenitor ◽  
Tensin Homolog

Background. Shear stress is an effective modulator of endothelial progenitor cells (EPCs) and has been suggested to play an important role in angiogenesis. The phosphatase and tensin homolog (PTEN)/Akt and guanosine triphosphate cyclohydrolase (GTPCH)/tetrahydrobiopterin (BH4) pathways regulate the function of early EPCs. However, the role of these pathways in the shear stress-induced angiogenesis of late EPCs remains poorly understood. Therefore, we aim to investigate whether shear stress could upregulate the angiogenesis capacity of late EPCs and to further explore the possible underlying mechanisms. Methods. Late EPCs were subjected to laminar shear stress (LSS), and their in vitro migration, proliferation, and tube formation capacity were determined. In addition, the in vivo angiogenesis capacity was explored, along with the expression of molecules involved in the PTEN/Akt and GTPCH/BH4 pathways. Results. LSS elevated the in vitro activities of late EPCs, which were accompanied by downregulated PTEN expression, accelerated Akt phosphorylation, and GTPCH/BH4 pathway activation (all P<0.05). Following Akt inhibition, LSS-induced upregulated GTPCH expression, BH4, and NO level of EPCs were suppressed. LSS significantly improved the migration, proliferation, and tube formation ability (15 dyn/cm2 LSS vs. stationary: 72.2±5.5 vs. 47.3±7.3, 0.517±0.05 vs. 0.367±0.038, and 1.664±0.315 vs. 1±0, respectively; all P<0.05) along with the in vivo angiogenesis capacity of late EPCs, contributing to the recovery of limb ischemia. These effects were also blocked by Akt inhibition or GTPCH knockdown (P<0.05, respectively). Conclusions. This study provides the first evidence that shear stress triggers angiogenesis in late EPCs via the PTEN/Akt/GTPCH/BH4 pathway, providing a potential nonpharmacologic therapeutic strategy for promoting angiogenesis in ischemia-related diseases.

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.

scholarly journals Ox-LDL induced endothelial progenitor cells oxidative stress via p38/Keap1/Nrf2 pathway

2021 ◽  
Author(s):  
Qijun Jiang ◽  
Chengpeng Li ◽  
Zhigang Gong ◽  
Zhigang Li ◽  
Shifang Ding
Keyword(s):  
Oxidative Stress ◽  
Membrane Potential ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Nuclear Translocation ◽  
Tube Formation ◽  
Ros Generation ◽  
Endothelial Progenitor ◽  
Migration Ability ◽  
Nrf2 Pathway

Abstract Background In many studies, endothelial progenitor cells (EPCs) highly expressing antioxidant protein were induced oxidative stress and apoptosis by Oxidized-low density lipoprotein (ox-LDL). Nrf2 which was resently reported to regulate the antioxidant genes and cellular redox regulators was highly expressed in EPCs. However, its role in ox-LDL induced EPCs oxidative stress and apoptosis has not been fully illustrated. Methods EPCs isolated from human peripheral blood mononuclear cells were treated with different concentration of ox-LDL, Keap1 siRNA and a specific p38 MAPK inhibitor SB203580, then used to assay the whole cellular Nrf2 (total Nrf2, t-Nrf2), cytoplasmic Nrf2 (c-Nrf2), nuclear Nrf2 (n- Nrf2), NAD(P) H:quinone oxidoreductase 1 (NQO1) protein levels and Bax /Bcl-2 with western blot, NQO1 mRNA levels with RT-PCR, ROS level with H2DCF-DA, the loss/disruption of mitochondrial membrane potential (MMP) with JC-1, apoptosis with Annexin-V and PI,migration ability with transwell chambers and tube formation. Results The ox-LDL treatment decreased the n-Nrf2/Histone H3 to c-Nrf2/GAPDH ratio, NQO1 mRNA and protein expression levels. Treatment of ox-LDL enhanced the ROS production, induced loss of membrane potential, increase in cell shrinkage, pyknotic nuclei and apoptosis of EPCs. The Keap1 knockdown with Keap1 siRNA increased the nuclear translocation of Nrf2, the NQO1 mRNA and protein transcription levels, and prevented ox-LDL induced ROS generation and formation of JC-1 monomers. Treatment of ox-LDL increased the activation of p38. Pretreatment with SB203580 significantly eliminated ox-LDL induced the inhibition of Nrf2 nuclear translocation, the depression of the mRNA transcription levels of NQO-1, the ROS generation and the formation of JC-1 monomers in EPCs. The pretreatment of Keap1 siRNA decreased the Bax/Bcl-2 ratio which was increased by the treatment of ox-LDL in EPCs. The ox-LDL treatment decreased EPCs migration activity and tube formation. Whereas the pre-treatment with Keap1 siRNA preserved the migration ability and tube formation of EPCs Conclusion Ox-LDL induced EPCs oxidative stress and apoptosis via p38/Keap1/Nrf2 pathway.

β2AR-dependent signaling contributes to in-vivo reendothelialization capacity of endothelial progenitor cells by shear stress

2020 ◽  
Vol 38 (1) ◽  
pp. 82-94 ◽  
Author(s):  
Qingsong Hu ◽  
Tao Zhang ◽  
Yan Li ◽  
Jianyi Feng ◽  
Ruqiong Nie ◽  
...  
Keyword(s):  
Shear Stress ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
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.

scholarly journals Vulnerability to shear stress caused by altered peri-endothelial matrix is a key feature of Moyamoya disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Muneaki Matsuo ◽  
Satomi Nadanaka ◽  
Minami Soga ◽  
Taku Sugiyama ◽  
Shota Serigano ◽  
...  
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Moyamoya Disease ◽  
Internal Carotid ◽  
Terminal Portion ◽  
Endothelial Progenitor ◽  
Wall Shear ◽  
Thickened Intima

AbstractMoyamoya disease (MMD) is characterized by progressive bilateral stenotic changes in the terminal portion of the internal carotid arteries. Although RNF213 was identified as a susceptibility gene for MMD, the exact pathogenesis remains unknown. Immunohistochemical analysis of autopsy specimens from a patient with MMD revealed marked accumulation of hyaluronan and chondroitin sulfate (CS) in the thickened intima of occlusive lesions of MMD. Hyaluronan synthase 2 was strongly expressed in endothelial progenitor cells in the thickened intima. Furthermore, MMD lesions showed minimal staining for CS and hyaluronan in the endothelium, in contrast to control endothelium showing positive staining for both. Glycosaminoglycans of endothelial cells derived from MMD and control induced pluripotent stem cells demonstrated a decreased amount of CS, especially sulfated CS, in MMD. A computational fluid dynamics model showed highest wall shear stress values in the terminal portion of the internal carotid artery, which is the predisposing region in MMD. Because the peri-endothelial extracellular matrix plays an important role in protection, cell adhesion and migration, an altered peri-endothelial matrix in MMD may contribute to endothelial vulnerability to wall shear stress. Invading endothelial progenitor cells repairing endothelial injury would produce excessive hyaluronan and CS in the intima, and cause vascular stenosis.

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