scholarly journals Angiotensin II Attenuates the Bioactivities of Human Endothelial Progenitor Cells via Downregulation of β2-Adrenergic Receptor

2018 ◽  
Vol 2018 ◽  
pp. 1-11
Author(s):  
Seon Jin Lee ◽  
Da Yeon Kim ◽  
Jisoo Yun ◽  
Sung Hyun Choi ◽  
Seok Yun Jung ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Adrenergic Receptor ◽  
Renin Angiotensin System ◽  
Tube Formation ◽  
Functional Assay ◽  
Ang Ii ◽  
Short Term Treatment ◽  
Endothelial Progenitor

Cross talks between the renin-angiotensin system (RAS), sympathetic nervous system, and vascular homeostasis are tightly coordinated in hypertension. Angiotensin II (Ang II), a key factor in RAS, when abnormally activated, affects the number and bioactivity of circulating human endothelial progenitor cells (hEPCs) in hypertensive patients. In this study, we investigated how the augmentation of Ang II regulates adrenergic receptor-mediated signaling and angiogenic bioactivities of hEPCs. Interestingly, the short-term treatment of hEPCs with Ang II drastically attenuated the expression of beta-2 adrenergic receptor (ADRB2), but did not alter the expression of beta-1 adrenergic receptor (ADRB1) and Ang II type 1 receptor (AT1R). EPC functional assay clearly demonstrated that the treatment with ADRB2 agonists significantly increased EPC bioactivities including cell proliferation, migration, and tube formation abilities. However, EPC bioactivities were decreased dramatically when treated with Ang II. Importantly, the attenuation of EPC bioactivities by Ang II was restored by treatment with an AT1R antagonist (telmisartan; TERT). We found that AT1R binds to ADRB2 in physiological conditions, but this binding is significantly decreased in the presence of Ang II. Furthermore, TERT, an Ang II-AT1R interaction blocker, restored the interaction between AT1R and ADRB2, suggesting that Ang II might induce the dysfunction of EPCs via downregulation of ADRB2, and an AT1R blocker could prevent Ang II-mediated ADRB2 depletion in EPCs. Taken together, our report provides novel insights into potential therapeutic approaches for hypertension-related cardiovascular diseases.

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.

Nox2 siRNA Transfection Down Regulates VEGF Induced-Angiogenesis on Endothelial Progenitor Cells Which Are Derived From HCB

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5188-5188
Author(s):  
Eun-Sun Yoo ◽  
Yeung-Chul Mun ◽  
Eun Mi Nam ◽  
Kyoung Eun Lee ◽  
Jung Won Huh ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Western Blot ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Tube Formation ◽  
Sirna Transfection ◽  
Endothelial Progenitor ◽  
Intracellular Ros ◽  
Perk Expression

Abstract Abstract 5188 Background: Reactive oxygen species (ROS) such as superoxide and H2O2 have roles signaling for molecules on angiogenesis. NADPH oxidase Nox2 (gp91phox) is a major source of ROS. Previous, we had found that Nox2-based NADPH oxidase (gp91phox)-induced ROS may play important roles on EPCs migration and proliferation by VEGF (Blood. 2009;114:Abstract 1445). In the present study, we studied the impact of down-regulation of Nox2 on intracellular ROS level, proliferation, transmigration, and in vitro tube formation of HCB derived EPCs via Nox2 siRNA transfection. Methods: Outgrowing endothelial progenitor cells were established from mononuclear cells of human cord blood (Yoo et al, Stem cells. 2003;21:228-235) using EGM-2 media in a fibronectin-coated dish. EPCs were transfected with HiPerFection transfection reagent plus Nox2 siRNA or non-targeting control siRNA and cultured for 5 hours. 100ng/ml of VEGF was added to the transfected cells and cultured for overnight. Expression of Nox2 and pERK in the Nox2 siRNA transfected EPCs were detected by western blot analysis. Intracellular ROS level was analyzed by staining with 2, 7-dichlrodihydro-fluorescein-diacetate (H2DCF-DA) and flow cytometry. Transmigration against VEGF was performed using transwell system (Costar) and in vitro tube formation was assayed using In vitro angiogenesis kit (Chemicon). Results: Intracellular ROS level was increased during endothelial progenitor cell culture which were derived from HCB by VEGF treatment. Proliferation, in vitro tube formation matrigel assay and migration assay on endothelial progenitor cells using VEGF were decreased with Nox2 siRNA transfection when compared with that of control group. In western blot data, Nox2-based NADPH oxidase (gp91phox) was increased by VEGF and decreased by Nox2 siRNA transfection. VEGF induced pERK expression was also decreased by Nox2 siRNA transfection as well. Conclusions: Based on our studies, Nox2-based NADPH oxidase (gp91phox)-induced ROS may have important roles on proliferation in HCB induced EPCs by VEGF stimulation. Furthermore, Nox2 siRNA transfection into HCB derived EPC down-regulated intracellular ROS production and pERK expression. Our data may be useful finding the new therapeutic targets for ischemic heart and ischemic limb diseases by manipulating the level of intracellular ROS via Nox2. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Endothelial progenitor cells relationships with clinical and biochemical factors in a human model of blunted angiotensin II signaling

2011 ◽  
Vol 34 (9) ◽  
pp. 1017-1022 ◽  
Author(s):  
Lorenzo A Calò ◽  
Monica Facco ◽  
Paul A Davis ◽  
Elisa Pagnin ◽  
Lucia Dal Maso ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Human Model ◽  
Endothelial Progenitor ◽  
Angiotensin Ii Signaling

scholarly journals Angiotensin II induced the apoptosis of the endothelial progenitor cells by the caspase-3

Cell Research ◽  
2008 ◽  
Vol 18 (S1) ◽  
pp. S160-S160
Author(s):  
Yonggang Wu ◽  
Qiru Wang ◽  
Lamei Cheng ◽  
Jian Wang ◽  
Xuan Sun ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Caspase 3 ◽  
Endothelial Progenitor

Dynamic compression promotes proliferation and neovascular networks of endothelial progenitor cells in demineralized bone matrix scaffold seed

2012 ◽  
Vol 113 (4) ◽  
pp. 619-626 ◽  
Author(s):  
Zhan Kong ◽  
Jianjun Li ◽  
Qun Zhao ◽  
Zhendong Zhou ◽  
Xiangnan Yuan ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Demineralized Bone Matrix ◽  
Dynamic Compression ◽  
Bone Matrix ◽  
Tube Formation ◽  
Endothelial Progenitor ◽  
Demineralized Bone

Neovascularization is required for bone formation and successful fracture healing. In the process of neovascularization, endothelial progenitor cells (EPCs) play an important role and finish vascular repair through reendothelialization to promote successful fracture healing. In this study, we found that dynamic compression can promote the proliferation and capillary-like tube formation of EPCs in the demineralized bone matrix (DBM) scaffold seed. EPCs isolated from the bone marrow of rats have been cultured in DBM scaffolds before dynamic compression and then seeded in the DBM scaffolds under dynamic conditions. The cells/scaffold constructs were subjected to cyclic compression with 5% strain and at 1 Hz for 4 h/day for 7 consecutive days. By using MTT and real-time PCR, we found that dynamic compression can significantly induce the proliferation of EPCs in three-dimensional culture with an even distribution of cells onto DBM scaffolds. Both in vitro and in vivo, the tube formation assays in the scaffolds showed that the loaded EPCs formed significant tube-like structures. These findings suggest that dynamic compression promoted the vasculogenic activities of EPCs seeded in the scaffolds, which would benefit large bone defect tissue engineering.

miR-126 modulates angiogenic growth parameters of peripheral blood endothelial progenitor cells

2015 ◽  
Vol 396 (3) ◽  
pp. 245-252 ◽  
Author(s):  
Sebastian M. Goerke ◽  
Lena S. Kiefer ◽  
G. Björn Stark ◽  
Filip Simunovic ◽  
Günter Finkenzeller
Keyword(s):  
Tissue Engineering ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Peripheral Blood ◽  
Growth Parameters ◽  
Therapeutic Option ◽  
Tube Formation ◽  
Loss Of Function ◽  
Endothelial Progenitor

Abstract Vascularization plays an important role in tissue engineering applications. It is known that implantation of differentiated endothelial cells or endothelial progenitor cells (EPCs) from cord blood (cbEPCs) gives rise to the formation of a complex functional neovasculature, whereas EPCs isolated from peripheral blood (pbEPCs) have a limited capability to form blood vessels upon implantation. MicroRNA-126 (miR-126) has been shown to have pro-angiogenic effects in vivo. In this study, we investigated whether modulation of miR-126 expression in pbEPCs may alter their angiogenic properties. Gain of function and loss of function experiments revealed that miR-126 has anti-angiogenic effects in pbEPCs. Overexpression of miR-126 resulted in decreased proliferation, migration, invasion and tube formation, while inhibition of miR-126 induced the opposite effects. However, modulation of miR-126 expression did not influence apoptotic susceptibility of pbEPCs. This study provides evidence that inhibition of miR-126 improves angiogenesis-related growth parameters in pbEPCs and may represent a therapeutic option to ameliorate the angiogenic and vasculogenic properties of pbEPCs.

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