Angiogenesis articles within Nature Communications

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  • Article
    | Open Access

    Tumors can overproduce pro-angiogenic ligands overcoming currently approved anti-angiogenic therapies and hindering their success. Here, the authors show that targeting phosphoinositide recycling during tumor angiogenesis harnesses the tumor’s own production of angiogenic ligands to deplete adjacent endothelial cells of the capacity to respond to these signals.

    • Amber N. Stratman
    • , Olivia M. Farrelly
    •  & Brant M. Weinstein

  • Article
    | Open Access

    The kidney is vascularized with highly specialized and zonated endothelial cells that are essential for its filtration function. Here, Barry et al. provide a single-cell RNA sequencing analysis of the kidney vasculature that highlights its transcriptional heterogeneity and uncovers pathways important for its development and function.

    • David M. Barry
    • , Elizabeth A. McMillan
    •  & Shahin Rafii

  • Article
    | Open Access

    Integrin-linked kinase (ILK) is an important mediator of integrin signaling. Here Park et al. show that mice with endothelial-specific deletion of Ilk develop vascular defects that resemble familial exudative vitreoretinopathy, and identify mutations in ILK in patients with exudative vitreoretinopathy suggesting a potential role in human pathogenesis.

    • Hongryeol Park
    • , Hiroyuki Yamamoto
    •  & Ralf H. Adams

  • Article
    | Open Access

    How coronary vessels develop and respond to injury is not fully understood. Here, the authors use murine enhancer:reporter models to identify three transcriptional pathways active in different parts of coronary vasculature. These also contribute to neovascularization in the injured neonatal, but not adult, heart.

    • Sophie Payne
    • , Mala Gunadasa-Rohling
    •  & Sarah De Val

  • Article
    | Open Access

    Pericytes are perivascular cells essential for blood-brain barrier maintenance. Here Diéguez-Hurtado et al. show that depletion of the transcription factor RBPJ in pericytes affects their molecular identity and disturbs endothelial cell behaviour, inducing the formation of vascular lesions in the brain.

    • Rodrigo Diéguez-Hurtado
    • , Katsuhiro Kato
    •  & Ralf H. Adams

  • Article
    | Open Access

    VEGF-A/VEGFR2 signaling is a key driver of endothelial cell migration during sprouting angiogenesis. Here Genet et al. show that endophilin A2 regulates these processes by mediating clathrin-independent VEGFR2 internalization.

    • Gael Genet
    • , Kevin Boyé
    •  & Anne Eichmann

  • Article
    | Open Access

    High mitogenic stimuli have been suggested to promote endothelial cell proliferation and sprouting during angiogenesis. Here Pontes-Quero et al., by interfering with levels of VEGF and Notch signalling in single endothelial cells in vivo, find that high mitogenic stimuli instead arrest angiogenesis due to a bell-shaped dose-response to VEGF and MAPK activity that is counteracted by Notch and p21.

    • Samuel Pontes-Quero
    • , Macarena Fernández-Chacón
    •  & Rui Benedito

  • Article
    | Open Access

    The growth factor VEGF is known to regulate vasculogenesis but the downstream pathways activated are unclear. Here, the authors report that Sec14l3, a member of the PITP (phosphatidyl inositol transfer proteins) family regulates the formation of zebrafish vasculature by promoting VEGFR2 endocytic trafficking.

    • Bo Gong
    • , Zhihao Li
    •  & Shunji Jia

  • Article
    | Open Access

    Proteoglycans are glycosylated proteins that play a number of structural and signalling functions. Here, Corti, Wang et al. show that the N-terminal sequence of proteoglycan Syndecan-2 selectively increases 6-O sulfation of its heparan sulfate chains, and that this promotes formation of a ternary Sdc2/VEGFA/VEGFR2 complex leading to increased angiogenesis.

    • Federico Corti
    • , Yingdi Wang
    •  & Michael Simons

  • Article
    | Open Access

    Chemically modified mRNA is a new approach for therapeutic protein expression that could be applied to angiogenesis. Here the authors show in a phase 1 clinical trial that a modified mRNA encoding VEGF-A is well tolerated in patients with type 2 diabetes.

    • Li-Ming Gan
    • , Maria Lagerström-Fermér
    •  & Regina Fritsche-Danielson

  • Article
    | Open Access

    Angiogenesis is driven by the directed migration of tip endothelial cells towards hypoxic tissues. Here, Kim et al. show that the generation of reactive oxygen species in endothelial cells upon hypoxia activates MST1, which subsequently promotes the nuclear translocation of FOXO1, and thus activates a pro-migratory transcriptional programme in endothelial tip cells.

    • Yoo Hyung Kim
    • , Jeongwoon Choi
    •  & Gou Young Koh

  • Article
    | Open Access

    Calcium signalling downstream of VEGF is essential for VEGF-induced angiogenesis. Here Savage et al. show that Transmembrane Protein 33 (TMEM33) is required for angiogenesis and the endothelial calcium response to VEGF, revealing a function for TMEM33 in multicellular organisms.

    • Aaron M. Savage
    • , Sathishkumar Kurusamy
    •  & Robert N. Wilkinson

  • Article
    | Open Access

    The establishment of functional vasculatures requires the specification of newly formed vessels into veins and arteries. Here, Neal et al. use a combination of genetic approaches in mice and zebrafish to show that BMP signalling, via ALK3 and SMAD1/5, is required for venous specification during blood vessel development.

    • Alice Neal
    • , Svanhild Nornes
    •  & Sarah De Val

  • Article
    | Open Access

    Wnt signaling is known to regulate the formation of the blood-brain barrier. Here Hübner et al. dissect the underlying mechanisms using high resolution live imaging in zebrafish, and find that Wnt regulates anastomosis of angiogenic sprouts in the brain by counteracting sphingosine-1-phosphate receptor signaling.

    • Kathleen Hübner
    • , Pauline Cabochette
    •  & Wiebke Herzog

  • Article
    | Open Access

    Angiogenesis requires dynamic endothelial rearrangements and relative position changes within the vascular tubes. Here the authors show that a PI3K/NUAK1/MYPT1/MLCP pathway regulates actomyosin contractility in endothelial cells and cellular rearrangement during vascular patterning.

    • Ana Angulo-Urarte
    • , Pedro Casado
    •  & Mariona Graupera

  • Article
    | Open Access

    During the formation of the zebrafish dorsal longitudinal anastomotic vessel, blood vessels connect in a process called anastomosis. Using live imaging, the authors here show that endothelial cell movements during blood vessel anastomosis are associated with oscillating lamellipodia-like structures, oriented in the direction of the movements and emerging at endothelial cell junctions.

    • Ilkka Paatero
    • , Loïc Sauteur
    •  & Heinz-Georg Belting

  • Article
    | Open Access

    Pericytes are perivascular cells that regulate blood vessel formation and function. Here Dubrac et al. show that pericyte recruitment contributes to pathological neovascularisation in a mouse model of ischemic retinopathy, and that this depends on the regulation of PDGF-B signaling by NCK adaptor proteins.

    • Alexandre Dubrac
    • , Steffen E. Künzel
    •  & Anne Eichmann

  • Article
    | Open Access

    The Hippo pathway is a major orchestrator of organ development and homeostasis. Here Azad and colleagues develop a biosensor to monitor the activity of the Hippo pathway component LATS and identify VEGF signalling as an upstream regulator of LATS, supporting a role for Hippo signalling during angiogenesis.

    • T. Azad
    • , H. J. Janse van Rensburg
    •  & X. Yang

  • Article
    | Open Access

    Heart development requires compaction of the ventricular wall into a dense myocardium at mid-gestation. Here, Rhee and colleagues show that the chromatin remodeller Ino80 is critical for the formation of the coronary vasculature, and show that coronary vessels are needed for successful cardiac compaction during embryonic development.

    • Siyeon Rhee
    • , Jae I. Chung
    •  & Kristy Red-Horse

  • Article
    | Open Access

    The formation of new blood vessels requires both polarized cell migration and coordinated control of endothelial cell contacts. Here, Cao and colleagues describe at the sub-cellular level the cytoskeletal and cell junction dynamics regulating these processes upon VEGF-induced cell elongation.

    • Jiahui Cao
    • , Manuel Ehling
    •  & Hans Schnittler

  • Article
    | Open Access

    New vessel formation relies on a tightly controlled switch in endothelial biology from proliferating to  specializing phenotypes. Here, Fang et al. elucidate the molecular mechanisms of this switch and show that the arterial shear activates a Notch-Cx37-p27 axis promoting endothelial cell cycle arrest and enabling arterial gene expression.

    • Jennifer S. Fang
    • , Brian G. Coon
    •  & Karen K. Hirschi

  • Article
    | Open Access

    Pericytes are essential for the development, maintenance and function of vascular networks. Here, Eilken and colleagues show that expression of the decoy receptor VEGFR1 by pericytes spatially restricts VEGF signalling, thus regulating VEGF-induced endothelial cell sprouting in developing tissues.

    • Hanna M. Eilken
    • , Rodrigo Diéguez-Hurtado
    •  & Ralf H. Adams

  • Article
    | Open Access

    Mechanical forces play a crucial role during morphogenesis, but how these are sensed and transduced in vivo is not fully understood. Here the authors apply a FRET tension sensor to live zebrafish and study changes in VE-cadherin tension at endothelial cell-cell junctions during arterial maturation.

    • Anne Karine Lagendijk
    • , Guillermo A. Gomez
    •  & Benjamin M. Hogan

  • Article
    | Open Access

    Molecular mechanisms of macrophage-mediated regulation of artery growth in response to ischemia are poorly understood. Here the authors show that vascular endothelium controls macrophage maturation and differentiation via Notch signaling, which in turn promotes arteriogenesis and ischemic tissue recovery.

    • Kashyap Krishnasamy
    • , Anne Limbourg
    •  & Florian P. Limbourg

  • Article
    | Open Access

    Angiogenesis is a complex process that requires coordinated changes in endothelial cell behavior. Here the authors use Ribo-tag and RNA-Seq to determine temporal profiles of transcriptional activity during postnatal retinal angiogenesis, identifying transcriptional regulators of the process.

    • Hyun-Woo Jeong
    • , Benjamín Hernández-Rodríguez
    •  & Ralf H. Adams

  • Article
    | Open Access

    Pathological angiogenesis in the retina is a major cause of blindness. Here the authors show that adenosine receptor A2A drives pathological angiogenesis in the oxygen-induced retinopathy mouse model by promoting glycolysis in endothelial cells via the ERK/Akt/HIF-1α pathway, thereby suggesting new therapeutic targets for disease treatment.

    • Zhiping Liu
    • , Siyuan Yan
    •  & Yuqing Huo

  • Article
    | Open Access

    Though coronary arteries are crucial for heart function, the mechanisms guiding their formation are largely unknown. Here, Wang et al. identify a unique, endocardially-derived angiogenic precursor cell population for coronary artery formation in mice and show that a DLL4/NOTCH1/VEGFA/VEGFR2 signaling axis is key for coronary artery development.

    • Yidong Wang
    • , Bingruo Wu
    •  & Bin Zhou

  • Article
    | Open Access

    Promoter proximal RNAPII pausing is a rate-limiting transcriptional mechanism. Chen et al. show that this process is essential in angiogenesis by demonstrating that the endothelial master transcription factor ETS1 promotes global RNAPII pause release, and that this process is governed by VEGF.

    • Jiahuan Chen
    • , Yi Fu
    •  & William T. Pu

  • Article
    | Open Access

    Abnormal angiogenesis causes many ocular diseases. Here the authors employ CRISPR/Cas9 gene editing technology to silence VEGFR2, a major regulator of angiogenesis, in retinal endothelium and abrogate angiogenesis in the mouse models of oxygen-induced retinopathy and laser-induced choroid neovascularization.

    • Xionggao Huang
    • , Guohong Zhou
    •  & Hetian Lei

  • Article
    | Open Access

    The angiopoietins regulate vascular maturation, angiogenesis and lymphangiogenesis via their Tie receptors that were long believed to be endothelium-specific. Here the authors show that angiopoietins activate and control pericyte function through pericyte-expressed Tie2 triggering of Calpain, Akt and FOXO3A signalling cascades.

    • Martin Teichert
    • , Laura Milde
    •  & Hellmut G. Augustin

  • Article
    | Open Access

    H-type endothelium, defined by the high expression of CD31 and endomucin, is found in the bone where it promotes angiogenesis and osteogensis. Here Yanget al. show that the miR-497∼195 cluster regulates the generation and maintenance of the H-type endothelium by controlling the levels of Notch regulator Fbxw7 and the HIF regulator P4HTM.

    • Mi Yang
    • , Chang-Jun Li
    •  & Xiang-Hang Luo

  • Article
    | Open Access

    Membrane-bound mVEGFR1 is a decoy VEGF-A receptor that regulates VEGF-A signalling amplitude. Boucheret al. show that Rab27a-regulated palmitoylation of mVEGFR1 redirects the receptor from a stable, constitutively recycling mode to a degradative route that removes ligands from the system.

    • Joshua M. Boucher
    • , Ryan P. Clark
    •  & Victoria L. Bautch

  • Article
    | Open Access

    The molecular mechanism regulating macrophage interaction with endothelial cells during development is unclear. Here, the authors show that in zebrafish mutation of hypoxia-inducible factor-1α impairs macrophage mobilization from the aorta-gonad-mesonephros, causing defects in angiogenesis and vessel repair.

    • Claudia Gerri
    • , Rubén Marín-Juez
    •  & Didier Y R. Stainier

  • Article
    | Open Access

    Foetal microchimeric cells (FMCs) are found in maternal circulation during pregnancy and migrate to injury sites, where they mediate repair, but how this is regulated is unclear. Here, the authors show in mice that the chemokine Ccl2 enhances delayed maternal wound healing through a subpopulation of Ccr2+ FMCs.

    • Mathieu Castela
    • , Dany Nassar
    •  & Selim Aractingi

  • Article
    | Open Access

    Blood-retinal barrier (BRB) is composed of tightly connected endothelium and supporting pericytes and glia. Here, the authors show that pericytes are crucial for BRB buildup during retinal development and its maintenance in adult retinas in response to VEGF-A-induced endothelial sensitization by regulating the Tie2/FOXO1/Ang2 axis.

    • Do Young Park
    • , Junyeop Lee
    •  & Gou Young Koh

  • Article
    | Open Access

    The guidance cues regulating blood vessel patterning in the central nervous system remain unclear. Here, the authors show in mice and chicken developing spinal cord that motor neurons control blood vessel patterning by an autocrine mechanism titrating VEGF via the expression of its trapping receptor sFlt1.

    • Patricia Himmels
    • , Isidora Paredes
    •  & Carmen Ruiz de Almodóvar

  • Article
    | Open Access

    Acute myocardial infarction (AMI) triggers sterile inflammatory reaction mediated by prostaglandin E2 (PGE2). Tang et al. show that the PGE2 via its receptor EP3 promotes cardiac healing after AMI by recruiting reparative Ly6Clowmonocytes/macrophages, which is mediated by TGF-β-driven regulation of CX3CR1 expression and VEGF secretion.

    • Juan Tang
    • , Yujun Shen
    •  & Ying Yu

  • Article
    | Open Access

    The generation of vasculature in organs is regulated by cross-talk between the developing tissue and specialized endothelial cells. Here, the authors show that vessel growth feeding the zebrafish spinal cord is coordinated by balancing neuron-derived pro-angiogenic ligand Vegfaa and its receptor, sFlt1.

    • Raphael Wild
    • , Alina Klems
    •  & Ferdinand le Noble

  • Article
    | Open Access

    Vasculature is denser in soft than in stiff tissues. Kragl et al. suggest a mechanistic link between biomechanical tissue properties and vascularization by showing that integrin-linked kinase reduces the contractile forces of the cell cortex in endocrine pancreatic cells, facilitating their adhesion to blood vessels and enabling pancreatic islet vascularization.

    • Martin Kragl
    • , Rajib Schubert
    •  & Eckhard Lammert

  • Article
    | Open Access

    Bone development and vascularization are coupled events that share many molecular mechanisms. Here the authors identify osteoblast-secreted Cxcl9 as an inhibitory regulator of angiogenesis and osteogenesis, and show that mTORC1 signaling and STAT1 are critical upstream mediators of the cytokine expression.

    • Bin Huang
    • , Wenhao Wang
    •  & Xiaochun Bai

  • Article
    | Open Access

    Formation of new blood vessels and bone is coupled. Here the authors show that blood flow represents a key regulator of angiogenesis and endothelial Notch signalling in the bone, and that reactivation of Notch signalling in the endothelium of aged mice rejuvenates the bone.

    • Saravana K. Ramasamy
    • , Anjali P. Kusumbe
    •  & Ralf H. Adams

  • Article
    | Open Access

    Arteriovenous malformations (AVM) is a hallmark of hereditary haemorrhagic telangiectasia type 2, a disease caused by mutations in BMP receptor ALK1. Ola et al. show that AVM can be caused by blocking BMP9 and BMP10 in mice, leading to increased VEGF and PI3K activity, and that pharmacologic inhibition of PI3K prevents AVM development.

    • Roxana Ola
    • , Alexandre Dubrac
    •  & Anne Eichmann

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