scholarly journals Blood flow coordinates collective endothelial cell migration during vascular plexus formation and promotes angiogenic sprout regression via vegfr3/flt4

2021 ◽  
Author(s):  
Yan Chen ◽  
Zhen Jiang ◽  
Katherine H Fisher ◽  
Hyejeong Rosemary Kim ◽  
Paul C Evans ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Blood Vessels ◽  
Endothelial Cell Migration ◽  
Vascular Networks ◽  
Vascular Remodelling ◽  
Venous Plexus ◽  
Vascular Plexus ◽  
And Migration

Nascent vascular networks adapt to the increasing metabolic demands of growing tissues by expanding via angiogenesis. As vascular networks expand, blood vessels remodel, progressively refining vascular connectivity to generate a more haemodynamically efficient network. This process is driven by interplay between endothelial cell (EC) signalling and blood flow. While much is known about angiogenesis, considerably less is understood of the mechanisms underlying vessel remodelling by blood flow. Here we employ the zebrafish sub-intestinal venous plexus (SIVP) to characterise the mechanisms underlying blood flow-dependent remodelling. Using live imaging to track ECs we show that blood flow controls SIVP remodelling by coordinating collective migration of ECs within the developing plexus. Blood flow opposes continuous ventral EC migration within the SIVP and is required for regression of angiogenic sprouts to support plexus growth. Sprout regression occurs by coordinated polarisation and migration of ECs from non-perfused leading sprouts, which migrate in opposition to blood flow and incorporate into the SIV. Sprout regression is compatible with low blood flow and is dependent upon vegfr3/flt4 function under these conditions. Blood flow limits expansive venous remodelling promoted by vegfr3/flt4. Collectively, these studies reveal how blood flow sculpts a developing vascular plexus by coordinating EC migration and balancing vascular remodelling via vegfr3/flt4

scholarly journals A Mathematical Model of anIn VitroExperiment to Investigate Endothelial Cell Migration

2002 ◽  
Vol 4 (4) ◽  
pp. 251-270 ◽  
Author(s):  
M. J. Plank ◽  
B. D. Sleeman ◽  
P. F. Jones
Keyword(s):  
Mathematical Model ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Blood Vessels ◽  
Three Dimensional ◽  
Cell Movement ◽  
Quantitative Model ◽  
Angiogenic Factors ◽  
Endothelial Cell Migration ◽  
Angiogenic Factor

Angiogenesis, the growth of new blood vessels from existing ones, is an important, yet not fully understood, process and is involved in diseases such as rheumatoid arthritis, diabetic retinopathy and solid tumour growth. Central to the process of angiogenesis are endothelial cells (EC), which line all blood vessels, and are capable of forming new capillaries by migration, proliferation and lumen formation. We construct a cell-based mathematical model of an experiment (Vernon, R.B. and Sage, E.H. (1999) “A novel, quantitative model for study of endothelial cell migration and sprout formation within three-dimensional collagen matrices”,Microvasc. Res.57, 118–133) carried out to assess the response of EC to various diffusible angiogenic factors, which is a crucial part of angiogenesis. The model for cell movement is based on the theory of reinforced random walks and includes both chemotaxis and chemokinesis. Three-dimensional simulations are run and the results correlate well with the experimental data. The experiment cannot easily distinguish between chemotactic and chemokinetic effects of the angiogenic factors. We, therefore, also run two-dimensional simulations of a hypothetical experiment, with a point source of angiogenic factor. This enables directed (gradient-driven) EC migration to be investigated independently of undirected (diffusion-driven) migration.

scholarly journals Sphingosine 1-Phosphate-induced Endothelial Cell Migration Requires the Expression of EDG-1 and EDG-3 Receptors and Rho-dependent Activation of αvβ3- and β1-containing Integrins

2001 ◽  
Vol 276 (15) ◽  
pp. 11830-11837 ◽  
Author(s):  
Ji H. Paik ◽  
Sung-suk Chae ◽  
Menq-Jer Lee ◽  
Shobha Thangada ◽  
Timothy Hla
Keyword(s):  
Cell Migration ◽  
Endothelial Cell ◽  
Molecular Mechanisms ◽  
Cell Attachment ◽  
Endothelial Cell Migration ◽  
Endothelial Differentiation ◽  
Focal Contact ◽  
Sphingosine 1 Phosphate ◽  
And Migration ◽  
Differentiation Gene

Sphingosine 1-phosphate (SPP), a platelet-derived bioactive lysophospholipid, is a regulator of angiogenesis. However, molecular mechanisms involved in SPP-induced angiogenic responses are not fully defined. Here we report the molecular mechanisms involved in SPP-induced human umbilical vein endothelial cell (HUVEC) adhesion and migration. SPP-induced HUVEC migration is potently inhibited by antisense phosphothioate oligonucleotides against EDG-1 as well as EDG-3 receptors. In addition, C3 exotoxin blocked SPP-induced cell attachment, spreading and migration on fibronectin-, vitronectin- and Matrigel-coated surfaces, suggesting that endothelial differentiation gene receptor signaling via the Rho pathway is critical for SPP-induced cell migration. Indeed, SPP induced Rho activation in an adherence-independent manner, whereas Rac activation was dispensible for cell attachment and focal contact formation. Interestingly, both EDG-1 and -3 receptors were required for Rho activation. Since integrins are critical for cell adhesion, migration, and angiogenesis, we examined the effects of blocking antibodies against αvβ3, β1, or β3integrins. SPP induced Rho-dependent integrin clustering into focal contact sites, which was essential for cell adhesion, spreading and migration. Blockage of αvβ3- or β1-containing integrins inhibited SPP-induced HUVEC migration. Together our results suggest that endothelial differentiation gene receptor-mediated Rho signaling is required for the activation of integrin αvβ3as well as β1-containing integrins, leading to the formation of initial focal contacts and endothelial cell migration.

scholarly journals Vascular-mesenchymal cross-talk through Vegf and Pdgf drives organ patterning

2010 ◽  
Vol 108 (1) ◽  
pp. 167-172 ◽  
Author(s):  
Jonah Cool ◽  
Tony J. DeFalco ◽  
Blanche Capel
Keyword(s):  
Cell Migration ◽  
Endothelial Cell ◽  
Blood Vessels ◽  
Cross Talk ◽  
De Novo ◽  
Endothelial Cell Migration ◽  
Vegf Signaling ◽  
Vessel Maturation ◽  
Endothelial Migration ◽  
Testis Cord

The initiation of de novo testis cord organization in the fetal gonad is poorly understood. Endothelial cell migration into XY gonads initiates testis morphogenesis. However, neither the signals that regulate vascularization of the gonad nor the mechanisms through which vessels affect tissue morphogenesis are known. Here, we show that Vegf signaling is required for gonad vascularization and cord morphogenesis. We establish that interstitial cells express Vegfa and respond, by proliferation, to endothelial migration. In the absence of vasculature, four-dimensional imaging of whole organs revealed that interstitial proliferation is reduced and prevents formation of wedge-like structures that partition the gonad into cord-forming domains. Antagonizing vessel maturation also reduced proliferation. However, proliferation of mesenchymal cells was rescued by the addition of PDGF-BB. These results suggest a pathway that integrates initiation of vascular development and testis cord morphogenesis, and lead to a model in which undifferentiated mesenchyme recruits blood vessels, proliferates in response, and performs a primary function in the morphogenesis and patterning of the developing organ.

scholarly journals PolNet Analysis: a software tool for the quantification of network-level endothelial cell polarity and blood flow during vascular remodelling

2017 ◽  
Author(s):  
Miguel O. Bernabeu ◽  
Martin L. Jones ◽  
Rupert W. Nash ◽  
Anna Pezzarossa ◽  
Peter V. Coveney ◽  
...  
Keyword(s):  
Blood Flow ◽  
Endothelial Cell ◽  
Cell Polarity ◽  
Software Tool ◽  
Vascular Networks ◽  
Vascular Patterning ◽  
And Migration ◽  
First Time ◽  
Analysis Protocol

AbstractIn this paper, we present PolNet, an open source software tool for the study of blood flow and cell-level biological activity during vessel morphogenesis. We provide an image acquisition, segmentation, and analysis protocol to quantify endothelial cell polarity in entire in vivo vascular networks. In combination, we use computational fluid dynamics to characterise the haemodynamics of the vascular networks under study. The tool enables, for the first time, network-level analysis of polarity and flow for individual endothelial cells. To date, PolNet has proven invaluable for the study of endothelial cell polarisation and migration during vascular patterning, as demonstrated by our recent papers [1, 2]. Additionally, the tool can be easily extended to correlate blood flow with other experimental observations at the cellular/molecular level. We release the source code of our tool under the LGPL licence.

scholarly journals TAK1 kinase signaling regulates embryonic angiogenesis by modulating endothelial cell survival and migration

Blood ◽  
2012 ◽  
Vol 120 (18) ◽  
pp. 3846-3857 ◽  
Author(s):  
Sho Morioka ◽  
Maiko Inagaki ◽  
Yoshihiro Komatsu ◽  
Yuji Mishina ◽  
Kunihiro Matsumoto ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Blood Vessels ◽  
Tube Formation ◽  
Cytokine Signaling ◽  
Capillary Networks ◽  
Endothelial Cell Death ◽  
And Migration ◽  
Multiple Abnormalities

Abstract TGF-β activated kinase 1 (TAK1) is a mediator of various cytokine signaling pathways. Germline deficiency of Tak1 causes multiple abnormalities, including dilated blood vessels at midgestation. However, the mechanisms by which TAK1 regulates vessel formation have not been elucidated. TAK1 binding proteins 1 and 2 (TAB1 and TAB2) are activators of TAK1, but their roles in embryonic TAK1 signaling have not been determined. In the present study, we characterized mouse embryos harboring endothelial-specific deletions of Tak1, Tab1, or Tab2 and found that endothelial TAK1 and TAB2, but not TAB1, were critically involved in vascular formation. TAK1 deficiency in endothelial cells caused increased cell death and vessel regression at embryonic day 10.5 (E10.5). Deletion of TNF signaling largely rescued endothelial cell death in TAK1-deficient embryos at E10.5. However, embryos deficient in both TAK1 and TNF signaling still exhibited dilated capillary networks at E12.5. TAB2 deficiency caused reduced TAK1 activity, resulting in abnormal capillary blood vessels, similar to the compound deficiency of TAK1 and TNF signaling. Ablation of either TAK1 or TAB2 impaired cell migration and tube formation. Our results show that endothelial TAK1 signaling is important for 2 biologic processes in angiogenesis: inhibiting TNF-dependent endothelial cell death and promoting TNF-independent angiogenic cell migration.

scholarly journals SAT-735 Effects of Androgen Receptor Activation on Angiogenesis

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Yen-Nien Huo
Keyword(s):  
Cell Migration ◽  
Androgen Receptor ◽  
Endothelial Cell ◽  
Signaling Pathway ◽  
Receptor Activation ◽  
Endothelial Cell Migration ◽  
Endothelial Cell Proliferation ◽  
Pre Treatment ◽  
And Migration ◽  
Proliferation And Migration

Abstract The effect of androgen on angiogenesis has been documented. However, its molecular mechanisms underlying has not been well illustrated. Here, we conducted both in vitro migration assay and proliferation assay to investigate whether androgen receptor activation have any impacts on the angiogenesis. Treatment with an androgen receptor (AR) agonist, metribolone (R1881) at a range of concentrations (0.05-5 nM) or dihydrotestosterone (DHT) at a range of concentrations (0.5-2 nM) caused concentration-dependent inhibition of proliferation and migration in human umbilical venous endothelial cells (HUVEC). Blockade of the AR activity by pre-treatment with HF (5 nM), an AR antagonist, or knockdown of AR expression using the lenti-virus shRNA technique abolished the R1881-induced proliferation and migration inhibition in HUVEC, suggesting that AR receptor activation can inhibit endothelial cell proliferation and migration. To further delineate the signaling pathway involved in the AR activation-induced proliferation inhibition, our data indicate that R1881 inhibited proliferation in vascular endothelial cells through activating the AR/cSrc/AKT/p38/ERK/NFκB signaling pathway, which in turn up-regulated the expression of p53, p21 and p27 protein, and finally reduced endothelial cell proliferation. To investigate signaling pathway involved in the AR activation-induced migration inhibition, our data showed that R1881 can reduce the membrane translocation of RhoA and Rac-1, suggesting that inhibition of the RhoA and Rac-1 activity might be involved in the R1881-inhibited endothelial cell migration. Over-expression of RhoA prevented the R1881-inhibited endothelial cell migration and this effect was abolished by pre-treatment with Y27623, a ROCK inhibitor, confirming that inhibiting RhoA activity participated in the R1881-inhibited endothelial cell migration. Using the zebrafish and Matrigel angiogenesis models, we also demonstrated that R1881 inhibited angiogenesis through the AR-mediated pathway in vivo.

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