Platelet-Derived Exosomes Affect the Proliferation and Migration of Human Umbilical Vein Endothelial Cells Via miR-126

2019 ◽  
Vol 17 (4) ◽  
pp. 379-387 ◽  
Author(s):  
Yan Sun ◽  
Xiao-li Liu ◽  
Dai Zhang ◽  
Fang Liu ◽  
Yu-jing Cheng ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Real Time ◽  
Umbilical Vein ◽  
Angiogenic Factors ◽  
Healthy Donors ◽  
And Migration ◽  
Umbilical Vein Endothelial Cells ◽  
Tgf Β1 ◽  
Proliferation And Migration

Background:Intraplaque angiogenesis, the process of generating new blood vessels mediated by endothelial cells, contributes to plaque growth, intraplaque hemorrhage, and thromboembolic events. Platelet-derived Exosomes (PLT-EXOs) affect angiogenesis in multiple ways. The ability of miR-126, one of the best-characterized miRNAs that regulates angiogenesis, carried by PLT-EXOs to influence angiogenesis via the regulation of the proliferation and migration of endothelial cells is unknown. In this study, we aimed to investigate the effects of PLT-EXOs on angiogenesis by Human Umbilical Vein Endothelial Cells (HUVECs).Methods:We evaluated the levels of miR-126 and angiogenic factors in PLT-EXOs from Acute Coronary Syndrome (ACS) patients and healthy donors by real-time Polymerase Chain Reaction (PCR) and western blotting. We incubated HUVECs with PLT-EXOs and measured cell proliferation and migration with the Cell Counting Kit-8 assay and scratch assay, respectively. We also investigated the expression of miR-126 and angiogenic factors in HUVECs after exposure to PLT-EXOs by western blotting and real-time PCR.Results:PLT-EXOs from ACS patients contained higher levels of miR-126 and angiogenic factors, including Vascular Endothelial Growth Factor (VEGF), basic Fibroblast Growth Factor (bFGF), and Transforming Growth Factor Beta 1 (TGF-β1), than those from healthy donors (p<0.05). Moreover, the levels of exosomal miR-126 and angiogenic factors were increased after stimulation with thrombin (p<0.01). HUVEC proliferation and migration were promoted by treatment with activated PLT-EXOs (p<0.01); they were accompanied by the over-expression of miR-126 and angiogenic factors, including VEGF, bFGF, and TGF-β1 (p<0.01).Conclusion:Activated PLT-EXOs promoted the proliferation and migration of HUVECs, and the overexpression of miR-126 and angiogenic factors, thereby elucidating potential new therapeutic targets for intraplaque angiogenesis.

Extract of Housefly (Musca domestica) Maggot Anti-Inflammatory Parts could Regulate the Proliferation and Migration of TNF-α- Stimulated Human Umbilical Vein Endothelial Cells

2014 ◽  
Vol 884-885 ◽  
pp. 446-449
Author(s):  
Fu Jiang Chu ◽  
Hong Yan Ma ◽  
Xiao Bao Jin ◽  
Jia Yong Zhu
Keyword(s):  
Endothelial Cells ◽  
Treatment Group ◽  
Umbilical Vein ◽  
House Fly ◽  
Human Umbilical Vein ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
And Migration ◽  
Umbilical Vein Endothelial Cells ◽  
Proliferation And Migration

House fly maggot, Musca domestica (Linnaeus) (Diptera: Muscidae) is one of the traditional Chinese medicine (TCM). In our earlier studies, the anti-inflammatory and anti-atherosclerotic functions of the housefly maggot have been found and also the anti-inflammatory effective parts have been acquired. In this study, the effect of housefly maggot anti-inflammatory parts on proliferation and migration of TNF-α-stimulated human umbilical vein endothelial cells (HUVEC) were investigated. And the results showed that the proliferation index and the migration rates of HUVEC which stimulated by TNF-α were decreased significantly in housefly maggot anti-inflammatory parts treatment group. And also the secretion of vascular endothelial growth factor (VEGF) was decreased too compared with only TNF-α treatment group. Based on the above, the housefly maggot anti-inflammatory parts could regulate the endothelial cell dysfunction through decreasing cell proliferation and migration and a reduction in VEGF expression might plays a key role in this process.

Transforming Growth Factor Betal and Beta2 Induce Down-Modulation of Thrombomodulin in Human Umbilical Vein Endothelial Cells

1995 ◽  
Vol 73 (05) ◽  
pp. 812-818 ◽  
Author(s):  
Taro Ohji ◽  
Hajime Urano ◽  
Akira Shirahata ◽  
Minoru Yamagishi ◽  
Ken Higashi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Time Course ◽  
Transforming Growth Factor ◽  
Umbilical Vein ◽  
Mrna Levels ◽  
Antigen Level ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells ◽  
Tgf Β1

SummaryTo investigate the effects of transforming growth factor-betas (TGF-βs) on endothelial anticoagulant activity, we assayed thrombomodulin (TM) activity and antigen levels of human umbilical vein endothelial cells (HUVECs) incubated with TGF-βs in vitro. TGF-β1 suppressed surface TM activity and surface TM antigen levels maximally 12 h after incubation in dose-dependent manners. TGF-β2 was almost equipotent with TGF-β1 for the suppression of them. Both TGF-βs suppressed total TM antigen level in HUVECs, and the time course of the suppression was similar to that of the cell surface TM antigen level. The maximal reductions of TM mRNA levels by TGF-βs were observed at several hours ahead of those observed in both surface and total TM antigen levels, suggesting that the TGF-β-mediated suppression of TM antigen of HUVECs is primarily regulated at the TM mRNA level. Our present work suggests that the down-modulation of TM level induced by TGF-βs in HUVECs contributes in vivo to promoting the thrombogenesis either at the sites of injury of vessel walls, such as atherosclerotic lesions where TGF-β1 is released from platelets, smooth muscle cells and monocytes, or at neovascular walls in tumors secreting TGF-β2.

Role of the small GTPase Rap1 for integrin activity regulation in endothelial cells and angiogenesis

Blood ◽  
2009 ◽  
Vol 113 (2) ◽  
pp. 488-497 ◽  
Author(s):  
Guillaume Carmona ◽  
Stephan Göttig ◽  
Alessia Orlandi ◽  
Jürgen Scheele ◽  
Tobias Bäuerle ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Umbilical Vein ◽  
Critical Role ◽  
Limb Ischemia ◽  
Small Gtpase ◽  
And Migration ◽  
Umbilical Vein Endothelial Cells ◽  
Endothelial Growth Factor

Abstract Ras-associated protein 1 (Rap1), a small GTPase, attracted attention because of its involvement in several aspects of cell adhesion, including integrin- and cadherin-mediated adhesion. Yet, the role of Rap1 genes and of Rap1 effectors for angiogenesis has not been investigated. Human umbilical vein endothelial cells (HUVECs) express Rap1a and Rap1b mRNA. To determine the contribution of Rap1 activity for angiogenesis, we overexpressed Rap1GAP1, a GTPase-activating protein that inhibits Rap1 activity. Overexpression of Rap1GAP1 significantly blocked angiogenic sprouting and tube-forming activity of HUVECs as well as migration and integrin-dependent adhesion. Silencing of Rap1a, Rap1b, or both significantly blocked HUVECs sprouting under basal and basic fibroblast growth factor-stimulated conditions and reduced HUVEC migration and integrin-dependent adhesion. We found that Rap1a and Rap1b are essential for the conformational activation of β1-integrins in endothelial cells. Furthermore, silencing of Rap1a and Rap1b prevented phosphorylation of tyrosine 397 in focal adhesion kinase (FAK) and vascular endothelial growth factor-induced Akt1-activation. Rap1a−/−-deficient and Rap1a+/− heterozygote mice displayed reduced neovascularization after hind limb ischemia compared with wild-type mice. Silencing of RAPL significantly blocked the Rap1-induced sprouting of HUVECs, suggesting that the angiogenic activity of Rap1 is partly mediated by RAPL. Our data demonstrate a critical role of Rap1 in the regulation of β1-integrin affinity, adhesion, and migration in endothelial cells and in postnatal neovascularization.

scholarly journals Primary human endothelial cells secrete agents that reduce responsiveness to lysophosphatidic acid (LPA)

2012 ◽  
Vol 32 (4) ◽  
pp. 393-400 ◽  
Author(s):  
Eun Young Park ◽  
Andrius Kazlauskas
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Lysophosphatidic Acid ◽  
Umbilical Vein ◽  
Vascular Endothelial ◽  
Human Endothelial Cells ◽  
Lpa Receptor ◽  
And Migration ◽  
Endothelial Growth Factor ◽  
Proliferation And Migration

The plasma level of LPA (lysophosphatidic acid) (200–600 nM) is well within the range that promotes proliferation and migration of vascular ECs (endothelial cells), yet vessels are quiescent and stable. In this report, we considered one explanation for this paradox: that ECs secrete agents that attenuate responsiveness to LPA. Indeed, we observed that CM (conditioned medium) from confluent, quiescent cultures of primary HUVECs (human umbilical vein ECs) contained an agent that inhibited LPA-mediated signalling events and cellular responses. The putative inhibitor, which we tentatively call ILMR (inhibitor of LPA-mediated responsiveness) seemed to act on cells (instead of at the level of LPA) by suppressing the ability of LPA receptor 1 to signal. The amount and/or activity of ILMR was regulated by growth factors; exposing HUVECs to VEGF-A (vascular endothelial growth factor A), but not bFGF (basic fibroblast growth factor), reduced the amount and/or activity of ILMR in CM. We conclude that in addition to promoting angiogenesis directly, VEGF-A can also act indirectly by modulating the bioactivity of angiomodulators such as LPA.

scholarly journals Effect of Lentivirus-Mediated miR-499a-3p on Human Umbilical Vein Endothelial Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Huilei Zheng ◽  
Juan Li ◽  
Ying Chen ◽  
Danping Gong ◽  
Jianlin Wen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Human Umbilical Vein ◽  
Polymerase Chain ◽  
And Migration ◽  
Umbilical Vein Endothelial Cells ◽  
Cell Migration And Proliferation ◽  
Scratch Tests ◽  
Proliferation And Migration

Objective. To explore the possible role of miR-499a-3p in the function of primary human umbilical vein endothelial cells (HUVECs) and the expression of ADAM10 in primary HUVEC. Method. miR-499a-3p was first transfected into primary HUVECs via lentivirus vector. The viability, proliferation, and migration of stable transfected primary HUVEC were then determined by flow cytometry, CCK8 assays, scratch tests, and Transwell tests. The transcription of miR-499a-3p and ADAM10 was examined by reverse transcription-polymerase chain reaction (RT-PCR), and the expression of ADAM10 was examined by Western blot (WB). Results. After transfection, miR-499a-3p transcription was significantly increased (P<0.01), compared to the blank and nonspecific control (NC) groups, while both ADAM10 transcription and expression were significantly decreased (P<0.05). In contrast, in the inhibitors group, miR-499a-3p transcription was significantly reduced (P<0.05) whereas both ADAM10 transcription and expression were significantly increased (P<0.05). The viability, proliferation, and migration of primary HUVECs were significantly impaired (P<0.05) by the transfection of miR-499a-3p but enhanced by miR-499a-3p inhibitors (P<0.05). Conclusions. Upregulation of miR-499a-3p transcription will inhibit the expression of ADAM10 in HUVECs; cell migration and proliferation, however, promote apoptosis. And reverse effects were established by downregulation of miR-499a-3p transcription. All these effects may be achieved by regulating the transcription and expression of ADAM10. These results combined suggested that miR-499a-3p may affect the proliferation, migration, and apoptosis of endothelial cells and regulate AS by regulating ADAM10. miR-499a-3p may become a candidate biomarker for the diagnosis of unstable angina pectoris (UA).

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