Quercetin inhibits human microvascular endothelial cells viability, migration and tube-formation in vitro through restraining microRNA-216a

2019 ◽  
Vol 28 (6) ◽  
pp. 609-616 ◽  
Author(s):  
Xu Wang ◽  
Xia Xue ◽  
Haiqing Wang ◽  
Fei Xu ◽  
Zhenlei Xin ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tube Formation ◽  
Microvascular Endothelial Cells ◽  
Microvascular Endothelial

Hydroxysafflor yellow A promotes angiogenesis in rat brain microvascular endothelial cells injured by oxygen-glucose deprivation/reoxygenation(OGD/R) through SIRT1-HIF-1α-VEGFA signaling pathway

2021 ◽  
Vol 18 ◽  
Author(s):  
Juxuan Ruan ◽  
Lei Wang ◽  
Jiheng Dai ◽  
Jing Li ◽  
Ning Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Ischemia Reperfusion ◽  
Tube Formation ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Hydroxysafflor Yellow A ◽  
Microvascular Endothelial

Objective: Angiogenesis led by brain microvascular endothelial cells (BMECs) contributes to the remission of brain injury after brain ischemia reperfusion. In this study, we investigated the effects of hydroxysafflor yellow A(HSYA) on angiogenesis of BMECs injured by OGD/R via SIRT1-HIF-1α-VEGFA signaling pathway. Methods: The OGD/R model of BMECs was established in vitro by OGD for 2h and reoxygenation for 24h. At first, the concentrations of vascular endothelial growth factor (VEGF), Angiopoietin (ang) and platelet-derived growth factor (PDGF) in supernatant were detected by ELISA, and the proteins expression of VEGFA, Ang-2 and PDGFB in BMECs were tested by western blot; the proliferation, adhesion, migration (scratch healing and transwell) and tube formation experiment of BMECs; the expression of CD31 and CD34 were tested by immunofluorescence staining. The levels of sirtuin1(SIRT1), hypoxia-inducible factor-1α (HIF-1α), VEGFA mRNA and protein were tested. Results: HSYA up-regulated the levels of VEGF, Ang and PDGF in the supernatant of BMECs under OGD/R, and the protein expression of VEGFA, Ang-2 and PDGFB were increased; HSYA could significantly alleviate the decrease of cell proliferation, adhesion, migration and tube formation ability of BMECs during OGD/R; HSYA enhanced the fluorescence intensity of CD31 and CD34 of BMECs during OGD/R; HSYA remarkably up-regulated the expression of SIRT1, HIF-1α, VEGFA mRNA and protein after OGD/R, and these increase decreased after SIRT1 was inhibited. Conclusion: SIRT1-HIF-1α-VEGFA signaling pathway is involved in HSYA improves angiogenesis of BMECs injured by OGD/R.

scholarly journals Tranilast inhibits the proliferation, chemotaxis and tube formation of human microvascular endothelial cells in vitro and angiogenesis in vivo

1997 ◽  
Vol 122 (6) ◽  
pp. 1061-1066 ◽  
Author(s):  
Masayuki Isaji ◽  
Hiroshi Miyata ◽  
Yoshiyuki Ajisawa ◽  
Yasuo Takehana ◽  
Nagahisa Yoshimura
Keyword(s):  
Endothelial Cells ◽  
Tube Formation ◽  
Microvascular Endothelial Cells ◽  
Microvascular Endothelial

scholarly journals Mucosal angiogenesis regulation by CXCR4 and its ligand CXCL12 expressed by human intestinal microvascular endothelial cells

2004 ◽  
Vol 286 (6) ◽  
pp. G1059-G1068 ◽  
Author(s):  
Jan Heidemann ◽  
Hitoshi Ogawa ◽  
Parvaneh Rafiee ◽  
Norbert Lügering ◽  
Christian Maaser ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Primary Cultures ◽  
Tube Formation ◽  
Microvascular Endothelial Cells ◽  
Endothelial Tube Formation ◽  
Microvascular Endothelial ◽  
Stromal Cell Derived Factor ◽  
Phosphoinositide 3 Kinase

Mice genetically deficient in the chemokine receptor CXCR4 or its ligand stromal cell-derived factor (SDF)-1/CXCL12 die perinatally with marked defects in vascularization of the gastrointestinal tract. The aim of this study was to define the expression and angiogenic functions of microvascular CXCR4 and SDF-1/CXCL12 in the human intestinal tract. Studies of human colonic mucosa in vivo and primary cultures of human intestinal microvascular endothelial cells (HIMEC) in vitro showed that the intestinal microvasculature expresses CXCR4 and its cognate ligand SDF-1/CXCL12. Moreover, SDF-1/CXCL12 stimulation of HIMEC triggers CXCR4-linked G proteins, phosphorylates ERK1/2, and activates proliferative and chemotactic responses. Pharmacological studies indicate SDF-1/CXCL12 evokes HIMEC chemotaxis via activation of ERK1/2 and phosphoinositide 3-kinase signaling pathways. Consistent with chemotaxis and proliferation, endothelial tube formation was inhibited by neutralizing CXCR4 or SDF-1/CXCL12 antibodies, as well as the ERK1/2 inhibitor PD-98059. Taken together, these data demonstrate an important mechanistic role for CXCR4 and SDF-1/CXCL12 in regulating angiogenesis within the human intestinal mucosa.

scholarly journals Endothelial Progenitor Cell-Derived Microvesicles Promote Angiogenesis in Rat Brain Microvascular Endothelial Cells In vitro

2021 ◽  
Vol 15 ◽  
Author(s):  
Wen Zeng ◽  
Qiaoling Lei ◽  
Jiao Ma ◽  
Shuqiang Gao ◽  
Rong Ju
Keyword(s):  
Endothelial Cells ◽  
Brain Injury ◽  
Tube Formation ◽  
Cell Counting ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Biological Functions ◽  
Endothelial Progenitor ◽  
Microvascular Endothelial

Brain microvascular endothelial cells (BMECs) are a major component of the blood-brain barrier that maintains brain homeostasis. Preserving and restoring the normal biological functions of BMECs can reverse or reduce brain injury. Endothelial progenitor cells (EPCs) may promote brain vascular remodeling and restore normal endothelial function. As a novel vehicle for cell-cell communication, microvesicles (MVs) have varied biological functions. The present study investigated the biological effects of EPC-derived MVs (EPC-MVs) on BMECs in vitro. We isolated MVs from the supernatant of EPCs in a serum-depleted medium. BMECs were cultured alone or in the presence of EPC-MVs. BMEC viability and proliferation were evaluated with the Cell Counting Kit-8 and by flow cytometry, and the proangiogenic effect of EPC-MVs on BMECs was assessed with the transwell migration, wound healing, and tube formation assays. Our results showed that EPC-derived MVs labeled with DiI were internalized by cultured BMECs; this enhanced BMEC viability and promoted their proliferation. EPC-MVs also stimulated migration and tube formation in BMECs. These results demonstrate that EPC-derived MVs exert a proangiogenic effect on BMECs, which has potential applications in cell-free therapy for brain injury.

Hypoxia in combination with FGF-2 induces tube formation by human microvascular endothelial cells in a fibrin matrix: involvement of at least two signal transduction pathways

2001 ◽  
Vol 114 (4) ◽  
pp. 825-833 ◽  
Author(s):  
M.E. Kroon ◽  
P. Koolwijk ◽  
B. van der Vecht ◽  
V.W. van Hinsbergh
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Tube Formation ◽  
Microvascular Endothelial Cells ◽  
Signal Pathways ◽  
Fibrin Matrix ◽  
Hypoxic Conditions ◽  
Mitogen Activated Protein ◽  
Microvascular Endothelial

Hypoxia in combination with a growth factor is a strong inducer of angiogenesis. Among several effects, hypoxia can activate endothelial cells directly, but the mechanism by which it acts is not fully elucidated. In vitro, human microvascular endothelial cells (hMVEC) form capillary-like tubules in fibrin solely after stimulation with a combination of fibroblast growth factor (FGF)-2 or vascular endothelial growth factor (VEGF) and the cytokine tumour necrosis factor (TNF)alpha. We show in this paper that in hypoxic conditions, FGF-2-stimulated hMVEC form tube-like structures in a fibrin matrix in the absence of TNFalpha. Hypoxia/FGF-2-stimulated cells express more urokinase-type plasminogen activator (u-PA) receptor than normoxia/FGF-2-stimulated cells and display a slightly higher turnover of u-PA. This small increase in u-PA activation probably cannot fully explain the hypoxia/FGF-2-induced tube formation. Hypoxia activated at least two signal pathways that may contribute to the enhanced angiogenic response. In hypoxia/FGF-2-stimulated hMVEC the transcription factor p65 was activated and translocated to the nucleus, whereas in normoxia/FGF-2-stimulated cells p65 remained inactive. Furthermore, in hypoxic conditions, the amounts of phosphorylated mitogen-activated protein kinases ERK1/2 were increased compared to normoxic conditions. We conclude that hypoxia is able to activate different signal pathways in FGF-2-stimulated human endothelial cells, which may be involved in hypoxia-induced angiogenesis.

scholarly journals TAFI and Pancreatic Carboxypeptidase B Modulate In Vitro Capillary Tube Formation by Human Microvascular Endothelial Cells

2007 ◽  
Vol 27 (10) ◽  
pp. 2157-2162 ◽  
Author(s):  
Ana H.C. Guimarães ◽  
Nancy Laurens ◽  
Ester M. Weijers ◽  
Pieter Koolwijk ◽  
Victor W.M. van Hinsbergh ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Capillary Tube ◽  
Tube Formation ◽  
Microvascular Endothelial Cells ◽  
Carboxypeptidase B ◽  
Microvascular Endothelial

scholarly journals Cooperative effect of TNFalpha, bFGF, and VEGF on the formation of tubular structures of human microvascular endothelial cells in a fibrin matrix. Role of urokinase activity.

1996 ◽  
Vol 132 (6) ◽  
pp. 1177-1188 ◽  
Author(s):  
P Koolwijk ◽  
M G van Erck ◽  
W J de Vree ◽  
M A Vermeer ◽  
H A Weich ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Three Dimensional ◽  
Cell Number ◽  
Tube Formation ◽  
Microvascular Endothelial Cells ◽  
Tubular Structures ◽  
Amino Terminal ◽  
Microvascular Endothelial

In angiogenesis associated with tissue repair and disease, fibrin and inflammatory mediators are often involved. We have used three-dimensional fibrin matrices to investigate the humoral requirements of human microvascular endothelial cells (hMVEC) to form capillary-like tubular structures. bFGF and VEGF165 were unable to induce tubular structures by themselves. Simultaneous addition of one or both of these factors with TNFalpha induced outgrowth of tubules, the effect being the strongest when bFGF, VEGF165, and TNFalpha were added simultaneously. Exogenously added u-PA, but not its nonproteolytic amino-terminal fragment, could replace TNFalpha, suggesting that TNFalpha-induced u-PA synthesis was involved. Soluble u-PA receptor (u-PAR) or antibodies that inhibited u-PA activity prevented the formation of tubular structures by 59-99%. epsilon-ACA and trasylol which inhibit the formation and activity of plasmin reduced the extent of tube formation by 71-95%. TNFalpha or u-PA did not induce tubular structures without additional growth factors. bFGF and VEGF165 enhanced of the u-PAR by 72 and 46%, but TNFalpha itself also increased u-PAR in hMVEC by 30%. Induction of mitogenesis was not the major contribution of bFGF and VEGF165 because the cell number did not change significantly in the presence of TNFalpha, and tyrphostin A47, which inhibited mitosis completely, reduced the formation of tubular structures only by 28-36%. These data show that induction of cell-bound u-PA activity by the cytokine TNFalpha is required in addition to the angiogenic factors VEGF165 and/or bFGF to induce in vitro formation of capillary-like structures by hMVEC in fibrin matrices. These data may provide insight in the mechanism of angiogenesis as occurs in pathological conditions.

C-C Motif Chemokine 8 promotes angiogenesis in vascular endothelial cells

Vascular ◽  
2020 ◽  
pp. 170853812095997
Author(s):  
Song Xue ◽  
Hanfei Tang ◽  
Gefei Zhao ◽  
Yang Shen ◽  
Ethan Yibo Yang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Map Kinase ◽  
Chemokine Receptor ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Microvascular Endothelial Cells ◽  
Human Umbilical Vein ◽  
Microvascular Endothelial ◽  
Endothelium Cells

Objectives Angiogenesis is an important progress associated with several pathological situations. Several chemokines have been reported to act as regulators of angiogenesis. The current study aimed to find whether C-C Motif Chemokine 8 is involved in angiogenesis regulation. Methods To verify whether C-C Motif Chemokine 8 is related to angiogenesis in plaques, carotid plaques were collected from patients with severe carotid stenosis and analysed using CD31 immunohistochemistry and real-time PCR. To further clarify the relation between C-C Motif Chemokine 8 and angiogenesis, human umbilical vein endothelium cells and human dermal microvascular endothelial cells were treated with C-C Motif Chemokine 8 in the presence or absence of C-C motif chemokine receptor 2-Ab and extracellular regulated MAP kinase 1/2 inhibition (FR180204). Proliferation and migration of human umbilical vein endothelium cells and human dermal microvascular endothelial cells were examined with Cell Counting Kit-8 and Transwell chamber assay, respectively. In vitro angiogenesis stimulated by C-C Motif Chemokine 8 was examined using tube formation assay. Ex vivo and in vivo angiogenesis were assessed by mice aortic ring assay and Matrigel plug assay, respectively. C-C motif chemokine receptors of human umbilical vein endothelium cells were examined with real-time PCR, and C-C motif chemokine receptor 1, C-C motif chemokine receptor 2, extracellular regulated MAP kinase 1/2 and phosphorylation-extracellular regulated MAP kinase 1/2 were examined with western blotting assay. Results C-C Motif Chemokine 8 was increased in carotid plaques with severe angiogenesis in both RNA and protein level. C-C Motif Chemokine 8 (5 ng/ml) weakly increased human umbilical vein endothelium cell proliferation, but not on human dermal microvascular endothelial cells. Migration and tube formation could be induced by C-C Motif Chemokine 8 in both human umbilical vein endothelium cells and human dermal microvascular endothelial cells. In mice aortic ring assay and Matrigel plug assay, C-C Motif Chemokine 8 could promote angiogenesis compared to vehicle groups. Phosphorylation of extracellular regulated MAP kinase 1/2 was increased with C-C Motif Chemokine 8 stimulation. The migration and tube formation promoted by C-C Motif Chemokine 8 could be largely blocked by C-C motif chemokine receptor 2-Ab or extracellular regulated MAP kinase 1/2 inhibition (FR180204). Conclusions C-C Motif Chemokine 8 could promote both in vitro and in vivo angiogenesis. C-C motif chemokine receptor 2 played an important role in the activation of C-C Motif Chemokine 8 and extracellular regulated MAP kinase 1/2 signalling pathway was involved in this mechanism.

Abstract 325: Temporally Separated Administration of Proangiogenic Growth Factor Combination Promotes Angiogenesis in Both Diabetic and Nondiabetic Microvascular Endothelial Cells

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Hao H Chen ◽  
Yu Jin Kim ◽  
Christine Liao ◽  
Pratiek N Matkar ◽  
Wei J Cao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factors ◽  
Growth Factor ◽  
Vascular Complications ◽  
Tube Formation ◽  
Microvascular Endothelial Cells ◽  
Angiogenic Growth Factors ◽  
Microvascular Endothelial

Background: Diabetes mellitus is a chronic metabolic disease associated with various vascular complications. Various strategies to promote therapeutic angiogenesis in ischemic tissue including delivery of pro-angiogenic growth factors have shown disappointing results. Risk factors, such as diabetes, may adversely impact the response to angiogenic strategies and limit efficacy in vivo. We assessed the hypothesis that temporally separated delivery of multiple pro-angiogenic growth factors will improve the efficacy of the angiogenic response in the setting of both diabetes and non-diabetes in vitro. Methods: 96-well tissue culture plates were coated with 60 μL growth factor reduced Matrigel. After gelation, non-diabetic human dermal microvascular endothelial cells (HMVECs) and type-II diabetic cells (D-HMVECs) were plated at 1x104 cells/well with 100 μL basal media EBM-2 with 0.1% bovine serum, and incubated at 37°C. Combinations of growth factors including recombinant human VEGF (50 ng/mL), angiopoietin (Ang)-1 and -2 (250 ng/mL) were administrated at start of the assay and/or at 6 hours into the assay. Images were taken at 3, 6, 9, 12, 18 and 24 hours and used for tube formation quantification by Inverted Microscope at 10x magnification. Results: In untreated control, D-HVECs showed reduced tube formation in compared to HMVECs (n=12; p<0.001). Growth factors combination ‘VEGF and Ang-2 at start of the assay and Ang-1 at 6 hours showed the most significantly increased of tube formation when compared to single growth factor (to VEGF, Ang-1, 2; p<0.001) or growth factors combination without temporally separated delivery (to VEGF/Ang-1, VEGF/Ang-2; p<0.001) in both HMVEC and D-HMVEC. Conclusion: Diabetic endothelial cells showed impaired angiogenesis compared to non-diabetic endothelial cells. Combinations of temporally separated pro-angiogenic growth factors were able to optimize the angiogenic effects and yield the most significant efficacy in the setting of both diabetes and non-diabetes. Future studies will focus on in vivo temporally separated combinations of multiple growth factors.

scholarly journals Isookanin Inhibits PGE2-Mediated Angiogenesis by Inducing Cell Arrest through Inhibiting the Phosphorylation of ERK1/2 and CREB in HMEC-1 Cells

2021 ◽  
Vol 22 (12) ◽  
pp. 6466
Author(s):  
Yingji Xin ◽  
Kyungbaeg Roh ◽  
Eunae Cho ◽  
Deokhoon Park ◽  
Wankyunn Whang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Inflammatory Diseases ◽  
Inhibitory Effect ◽  
Biological Properties ◽  
Tube Formation ◽  
Microvascular Endothelial Cells ◽  
Potential Candidate ◽  
Creb Phosphorylation ◽  
Microvascular Endothelial ◽  
Cell Arrest

Inflammation is increasingly recognized as a critical mediator of angiogenesis, and unregulated angiogenic responses often involve human diseases. The importance of regulating angiogenesis in inflammatory diseases has been demonstrated through some successful cases of anti-angiogenesis therapies in related diseases, including arthritis, but it has been reported that some synthetic types of antiangiogenic drugs have potential side effects. In recent years, the importance of finding alternative strategies for regulating angiogenesis has begun to attract the attention of researchers. Therefore, identification of natural ingredients used to prevent or treat angiogenesis-related diseases will play a greater role. Isookanin is a phenolic flavonoid presented in Bidens extract, and it has been reported that isookanin possesses some biological properties, including antioxidative and anti-inflammatory effects, anti-diabetic properties, and an ability to inhibit α-amylase. However, its antiangiogenic effects and mechanism thereof have not been studied yet. In this study, our results indicate that isookanin has an effective inhibitory effect on the angiogenic properties of microvascular endothelial cells. Isookanin shows inhibitory effects in multiple stages of PGE2-induced angiogenesis, including the growth, proliferation, migration, and tube formation of microvascular endothelial cells. In addition, isookanin induces cell cycle arrest in S phase, which is also the reason for subsequent inhibition of cell proliferation. The mechanism of inhibiting angiogenesis by isookanin is related to the inhibition of PGE2-mediated ERK1/2 and CREB phosphorylation. These findings make isookanin a potential candidate for the treatment of angiogenesis-related diseases.

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