8 documents found, page 1 of 1
A 96-wells fluidic system for high-throughput screenings under laminar high wal...
Fonseca, Catarina Gonçalves; Silvério, Vânia; Barata, David; Giese, Wolfgang; Gerhardt, Holger; Cardoso, Susana; Franco, Cláudio AreiasThe ability of endothelial cells to respond to blood flow is fundamental for the correct formation and maintenance of a functional and hierarchically organized vascular network. Defective flow responses, in particular related to high flow conditions, have been associated with atherosclerosis, stroke, arteriovenous malformations, and neurodegenerative diseases. Yet, the molecular mechanisms involved in high flow...
A 96-wells fluidic system for high-throughput screenings under laminar high wal...
Fonseca, Catarina; Silvério, Vânia; Barata, David; Giese, Wolfgang; Gerhardt, Holger; Cardoso, Susana; Franco, ClaudioThe ability of endothelial cells to respond to blood flow is fundamental for the correct formation and maintenance of a functional and hierarchically organized vascular network. Defective flow responses, in particular related to high flow conditions, have been associated with atherosclerosis, stroke, arteriovenous malformations, and neurodegenerative diseases. Yet, the molecular mechanisms involved in high flow...
Tyrosine-protein kinase Yes controls endothelial junctional plasticity and barr...
Jin, Yi; Ding, Yindi; Richards, Mark; Kaakinen, Mika; Giese, Wolfgang; Baumann, Elisabeth; Szymborska, Anna; Rosa, André; Nordling, SofiaVascular endothelial (VE)-cadherin in endothelial adherens junctions is an essential component of the vascular barrier, critical for tissue homeostasis and implicated in diseases such as cancer and retinopathies. Inhibitors of Src cytoplasmic tyrosine kinase have been applied to suppress VE-cadherin tyrosine phosphorylation and prevent excessive leakage, edema and high interstitial pressure. Here we show that t...
On the preservation of vessel bifurcations during flow-mediated angiogenic remo...
Edgar, Lowell T.; Franco, Claudio; Gerhardt, Holger; Bernabeu, Miguel O.During developmental angiogenesis, endothelial cells respond to shear stress by migrating and remodelling the initially hyperbranched plexus, removing certain vessels whilst maintaining others. In this study, we argue that the key regulator of vessel preservation is cell decision behaviour at bifurcations. At flow-convergent bifurcations where migration paths diverge, cells must finely tune migration along both...
YAP and TAZ regulate adherens junction dynamics and endothelial cell distributi...
Neto, Filipa; Klaus-Bergmann, Alexandra; Ong, Yu Ting; Alt, Silvanus; Vion, Anne-Clémence; Szymborska, Anna; Carvalho, Joana R.; Hollfinger, IreneFormation of blood vessel networks by sprouting angiogenesis is critical for tissue growth, homeostasis and regeneration. How endothelial cells arise in adequate numbers and arrange suitably to shape functional vascular networks is poorly understood. Here we show that YAP/TAZ promote stretch-induced proliferation and rearrangements of endothelial cells whilst preventing bleeding in developing vessels. Mechanist...
Knockout of the PKN family of Rho effector kinases reveals a non-redundant role...
Quétier, Ivan; Marshall, Jacqueline J. T.; Spencer-Dene, Bradley; Lachmann, Sylvie; Casamassima, Adele; Franco, Claudio; Escuin, SarahIn animals, the protein kinase C (PKC) family has expanded into diversely regulated subgroups, including the Rho family-responsive PKN kinases. Here, we describe knockouts of all three mouse PKN isoforms and reveal that PKN2 loss results in lethality at embryonic day 10 (E10), with associated cardiovascular and morphogenetic defects. The cardiovascular phenotype was not recapitulated by conditional deletion of ...
FOXO1 couples metabolic activity and growth state in the vascular endothelium
Wilhelm, Kerstin; Happel, Katharina; Eelen, Guy; Schoors, Sandra; Oellerich, Mark F.; Lim, Radiance; Zimmermann, Barbara; Aspalter, Irene M.Endothelial cells (ECs) are plastic cells that can switch between growth states with different bioenergetic and biosynthetic requirements. Although quiescent in most healthy tissues, ECs divide and migrate rapidly upon proangiogenic stimulation. Adjusting endothelial metabolism to the growth state is central to normal vessel growth and function, yet it is poorly understood at the molecular level. Here we report...
Computer simulations reveal complex distribution of haemodynamic forces in a mo...
Bernabeu, Miguel O.; Jones, Martin; Nielsen, Jens H.; Krüger, Timm; Nash, Rupert W.; Groen, Derek; Schmieschek, Sebastian; Hetherington, JamesThere is currently limited understanding of the role played by haemodynamic forces on the processes governing vascular development. One of many obstacles to be overcome is being able to measure those forces, at the required resolution level, on vessels only a few micrometres thick. In this paper, we present an in silico method for the computation of the haemodynamic forces experienced by murine retinal vasculat...