scholarly journals Resveratrol Improves Tube Formation in AGE-Induced Late Endothelial Progenitor Cells by Suppressing Syndecan-4 Shedding

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Han Wu ◽  
Zheng Chen ◽  
Jian-Zhou Chen ◽  
Jun Xie ◽  
Biao Xu
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Human Peripheral Blood ◽  
Cardiovascular Complications ◽  
Tube Formation ◽  
Dependent Manner ◽  
Endothelial Progenitor ◽  
Heparin Sulfate Proteoglycan ◽  
Heparin Sulfate ◽  
A Cell

Dysfunction of endothelial progenitor cells (EPCs) contributes to cardiovascular complications in diabetes, and resveratrol has been shown to improve EPC functions. Syndecan-4 (Synd4), a cell surface heparin sulfate proteoglycan, has been shown to promote neovascularization. Thus, the present study was performed to determine whether resveratrol promoted angiogenesis of EPCs by regulating Synd4. Late EPCs were isolated from human peripheral blood and stimulated with AGEs. Western blot showed that AGEs induced Synd4 shedding in a dose- and time-dependent manner. AGE-induced Synd4 shedding was partly reversed by NAC or resveratrol, along with normalized ROS production. Overexpression of Synd4 or pretreatment of resveratrol reversed AGE-impaired tube formation of EPCs and regulated the Akt/eNOS pathway. Furthermore, resveratrol suppressed Synd4 shedding via the inhibition of oxidative stress and improved tube formation of late EPCs via the regulation of the Synd4/Akt/eNOS pathway.

Erythropoietin regulates endothelial progenitor cells

Blood ◽  
2004 ◽  
Vol 103 (3) ◽  
pp. 921-926 ◽  
Author(s):  
Ferdinand H. Bahlmann ◽  
Kirsten de Groot ◽  
Jens-Michael Spandau ◽  
Aimee L. Landry ◽  
Barbara Hertel ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Peripheral Blood ◽  
Healthy Subjects ◽  
Tube Formation ◽  
Dependent Manner ◽  
Endothelial Progenitor ◽  
Vitro Assay ◽  
Dose Dependent

AbstractCirculating bone marrow–derived endothelial progenitor cells (EPCs) promote vascular reparative processes and neoangiogenesis, and their number in peripheral blood correlates with endothelial function and cardiovascular risk. We tested the hypothesis that the cytokine erythropoietin (EPO) stimulates EPCs in humans. We studied 11 patients with renal anemia and 4 healthy subjects who received standard doses of recombinant human EPO (rhEPO). Treatment with rhEPO caused a significant mobilization of CD34+/CD45+ circulating progenitor cells in peripheral blood (measured by flow cytometry), and increased the number of functionally active EPCs (measured by in vitro assay) in patients (week 2, 312% ± 31%; week 8, 308% ± 40%; both P < .01 versus baseline) as well as in healthy subjects (week 8, 194% ± 15%; P < .05 versus baseline). The effect on EPCs was already observed with an rhEPO dose of about 30 IU/kg per week. Administration of rhEPO increased the number of functionally active EPCs by differentiation in vitro in a dose-dependent manner, assessed in cell culture and by tube formation assay. Furthermore, rhEPO activates the Akt protein kinase pathway in EPCs. Erythropoietin increases the number of functionally active EPCs in humans. Administration of rhEPO or EPO analogs may open new therapeutic strategies in regenerative cardiovascular medicine.

scholarly journals Asymmetric Dimethylarginine and Endothelial Progenitor Cells After Renal Transplantation: the Effect of Exercise Training

2014 ◽  
pp. S411-S417
Author(s):  
V. TEPLAN ◽  
I. KRÁLOVÁ LESNÁ ◽  
J. PIŤHA ◽  
A. MAHROVÁ ◽  
J. RACEK ◽  
...  
Keyword(s):  
Renal Transplantation ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Asymmetric Dimethylarginine ◽  
Exercise Program ◽  
Cardiovascular Complications ◽  
Hla Typing ◽  
Endothelial Progenitor ◽  
Group I ◽  
Group Ii

Level of asymmetric dimethylarginine (ADMA) is elevated and endothelial progenitor cells (EPC) and stem cells (SC) are decreased in patients undergoing renal transplantation (Tx) and may contribute to cardiovascular complications. We tested the hypothesis that ADMA, EPC and SC can be influenced with regular physical exercise early after Tx. Blood samples of ADMA, EPC, SC, adipocytokines and metabolic parameters were randomly obtained from 50 transplant patients before and 6 months after exercise program (Group I). Fifty age, sex, HLA typing, duration of dialysis and immunosupression regimen-matched non exercising transplant were examined as controls (Group II). After 6 months, in Group I ADMA decreased (3.50±0.45 vs 2.11±0.35 μmol/l, P<0.01) and was lower comparing to Group II (P<0.01), SC and EPC also decreased (2816±600 vs 2071±480 cells/ml resp. 194±87 to 125±67 cells/ml, P<0.02). Next changes in Group I: adiponectin (P<0.01), leptin (P<0.01), resistin (P<0.02). Visfatin, blood lipids, HbA1c, insulin and blood pressure were also influenced by training program (P<0.05).

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.

Abstract TP275: “Touch-and-Go”: Touching of Endothelial Cells by Endothelial Progenitor Cells Increases Activation of Pro-survival ERK1/2 Signaling

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Emiri T Mandeville ◽  
Su Jing Chen ◽  
Kazuhide Hayakawa ◽  
Ken Arai ◽  
Eng H Lo
Keyword(s):  
Endothelial Cells ◽  
Rat Brain ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Short Duration ◽  
Intracellular Signaling ◽  
Infarct Volume ◽  
Dependent Manner ◽  
Brain Endothelial Cells ◽  
Endothelial Progenitor

Background: Cell-based therapies can potentially promote neurological repair for CNS diseases including stroke. Pre-clinical data showed improved infarct volume and neurological scores following injection of Endothelial progenitor cells (EPCs). However relatively few EPCs were found in infarct areas, and mechanisms by which injected EPCs enhance neovascularization are largely unknown. In this study, we hypothesized that circulating EPCs would positively impact intracellular signaling cascades in rat brain endothelial cells (RBECs) even by short-duration contact due to activation of pro-survival ERK1/2 cascades. Methods: Primary RBECs and EPCs were isolated from rat brain and spleen, respectively. These cells were cultured separately, and 10 days later, cultured EPCs were transferred to plates of cultured RBECs. After 1 or 10 min incubation with cell-culture plate shaking, EPCs were washed from the plates and RBECs were subjected to western blot analysis to assess ERK1/2 phosphorylation. As a negative control for EPCs, we prepared neutrophils from different rats. Results: We confirmed that our RBECs and EPCs were viable in vitro by LDH assay and these cells were positive for their cell-type markers assessed by immunostaining. Ten min incubation of EPCs phosphorylated ERK1/2 in RBECs in an EPC-number-dependent manner, whereas identical conditions of neurtrophil incubation did not. Importantly, only 1 min incubation with EPCs significantly upregulated ERK cascades in RBECs. Remaining EPCs on RBEC surfaces may not contribute to ERK1/2 phosphorylation because very few EPCs were observed after washout. In addition, experiments by the same procedure without RBECs did not show ERK phosphorylation. Conclusion: We demonstrated increased activation of pro-survival ERK1/2 signaling in RBECs following short-duration incubation of EPCs. Results suggest that circulating EPCs may not need to be integrated into existing blood vessels to promote neovascularization. Rather, short-duration interactions between EPCs and RBECs may provide a “Touch-and-Go” stimulus that supports brain endothelial cells to make favorable environments for neovascularization.

scholarly journals Protective Effect of Silymarin against Rapamycin-induced Apoptosis and Proliferation Inhibition in Endothelial Progenitor Cells

2015 ◽  
Vol 10 (2) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Peng Zhang ◽  
Guohua Han ◽  
Pei Gao ◽  
Kun Qiao ◽  
Yusheng Ren ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Mononuclear Cells ◽  
Control Group ◽  
Dependent Manner ◽  
Endothelial Progenitor ◽  
Concentration Dependent Manner ◽  
Inhibition Of Proliferation ◽  
And Migration ◽  
Proliferation And Migration

For this study, peripheral blood samples were collected from human volunteers. Mononuclear cells (MNC) were separated by density centrifugation and were induced to differentiate into endothelial progenitor cells (EPCs) in vitro. Different concentrations of rapamycin and silymarin were introduced to the EPCs over 24 hours and then EPCs were analyzed for proliferation, migration, apoptosis and angiogenesis. Compared with the control group, rapamycin (1, 10, 100 ng/mL) inhibited the proliferation and migration of EPCs in a concentration dependent manner ( P<0.05). Silymarin (50, 100 μg/mL) enhanced the proliferation and migration of EPCs and inhibited apoptosis in a concentration dependent manner ( P<0.05). By adding rapamycin (1 ng/mL) and silymarin (25, 50, 100 μg/mL) over 24 hours, silymarin inhibited the pro-apoptotic effect of rapamycin on EPCs, and reversed the inhibition of proliferation, migration and angiogenesis of EPCs by rapamycin ( P<0.05).

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 Diabetes, Endothelial Dysfunction, and Vascular Repair: What Should a Diabetologist Keep His Eye on?

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
V. Altabas
Keyword(s):  
Diabetes Mellitus ◽  
Endothelial Cells ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Vascular Diseases ◽  
Vascular Biology ◽  
Cardiovascular Complications ◽  
Endothelial Progenitor ◽  
Incurable Disease ◽  
Advanced Stages

Cardiovascular complications are the most common complications of diabetes mellitus. A prominent attribute of diabetic cardiovascular complications is accelerated atherosclerosis, considered as a still incurable disease, at least at more advanced stages. The discovery of endothelial progenitor cells (EPCs), able to replace old and injured mature endothelial cells and capable of differentiating into healthy and functional endothelial cells, has offered the prospect of merging the traditional theories on the pathogenesis of atherosclerosis with evolving concepts of vascular biology. The literature supports the notion that EPC alterations are involved in the pathogenesis of vascular diseases in diabetics, but at present many questions remain unanswered. In this review the aspects linking endothelial progenitor cells to the altered vascular biology in diabetes mellitus are discussed.

Soluble CD40 ligand impairs the anti-platelet function of peripheral blood angiogenic outgrowth cells via increased production of reactive oxygen species

2013 ◽  
Vol 109 (05) ◽  
pp. 940-947 ◽  
Author(s):  
Lara Khzam ◽  
Ahmed Hachem ◽  
Younes Zaid ◽  
Rahma Boulahya ◽  
Walid Mourad ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Platelet Aggregation ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Platelet Function ◽  
Peripheral Blood ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Endothelial Progenitor

SummaryAdult peripheral blood angiogenic early outgrowth cells (EOCs), also known as early endothelial progenitor cells, interact with other blood and vascular cells and may regulate atherothrombosis. We have previously shown that endothelial progenitor cells inhibit platelet function and thrombus formation. The CD40L/CD40 axis is a thrombo-inflammatory mediator that affects platelet and endothelial functions. It has been shown that EOCs express CD40, whereas platelets represent the major source of its soluble ligand (sCD40L), which impairs EOC function. We aimed to test the hypothesis that the sCD40L/CD40 axis affects the anti-platelet function of EOCs. Human peripheral blood mononuclear cell-derived EOCs in culture inhibited platelet aggregation. Pre-treatment of EOCs with sCD40L reduced their in-hibitory effect on platelet aggregation in a CD40-dependent manner. EOCs viability and release of the anti-aggregating agents, prostacyclin and nitric oxide, were not affected by sCD40L. However, production of reactive oxygen species (ROS) was increased in sCD40L–treated EOCs. Blockade of ROS reversed the effects of sCD40L–treated EOCs on platelet aggregation. This study reveals that the sCD40L/CD40 axis impairs the anti-platelet properties of EOCs through increased production of ROS. These data may explain the link between elevated levels of sCD40L, impaired activity of EOCs and enhanced platelet reactivity, and consequently the occurrence of atherothrombotic disease.

Sign in / Sign up

Export Citation Format

Share Document