ArticleArteriosclerosis, thrombosis, and vascular biology2014
Shear stress-activated Wnt-angiopoietin-2 signaling recapitulates vascular repair in zebrafish embryos.
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Article in Arteriosclerosis, thrombosis, and vascular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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39citing papers in PubMed
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39 citing papers in PubMed, 63 citations in OpenAlex.
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- Angiogenesis within atherosclerotic plaques: Mechanical regulation, molecular mechanism and clinical diagnosis.Mechanobiology in medicine · 2025Review
- Origin and flow-mediated remodeling of the murine and human extraembryonic circulation systems.Frontiers in physiology · 2024Review
- Angiopoietin-2 Promotes Mechanical Stress-induced Extracellular Matrix Degradation in Annulus Fibrosus Via the HIF-1α/NF-κB Signaling Pathway.Orthopaedic surgery · 2023Article
- Endothelial mechanobiology in atherosclerosis.Cardiovascular research · 2023Review
- Disturbed flow increases endothelial inflammation and permeability via a Frizzled-4-β-catenin-dependent pathway.Journal of cell science · 2023Article
- Mechanical regulation of the early stages of angiogenesis.Journal of the Royal Society, Interface · 2022Review
- Wnt/β-Catenin Signaling Pathway Is Strongly Implicated in Cadmium-Induced Developmental Neurotoxicity and Neuroinflammation: Clues from Zebrafish Neurobehavior and In Vivo Neuroimaging.International journal of molecular sciences · 2022Article
- Computational simulations of the 4D micro-circulatory network in zebrafish tail amputation and regeneration.Journal of the Royal Society, Interface · 2022Article
- Effects of Stress on Osteoblast Proliferation and Differentiation Based on Endoplasmic Reticulum Stress and WntContrast media & molecular imaging · 2022Article
- Nuclear Mechanosensation and Mechanotransduction in Vascular Cells.Frontiers in cell and developmental biology · 2022Review
- Vascular Injury in the Zebrafish Tail Modulates Blood Flow and Peak Wall Shear Stress to Restore Embryonic Circular Network.Frontiers in cardiovascular medicine · 2022Article
- Endothelial mechanotransduction in cardiovascular development and regeneration: emerging approaches and animal models.Current topics in membranes · 2021Review
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- Resident mesenchymal vascular progenitors modulate adaptive angiogenesis and pulmonary remodeling via regulation of canonical Wnt signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Endothelialization of arterial vascular grafts by circulating monocytes.Nature communications · 2020Article
- Endothelial responses to shear stress in atherosclerosis: a novel role for developmental genes.Nature reviews. Cardiology · 2020Review
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Authors and funding
16 authors at 1 institution in 1 country.
Rongsong LiFrom the Department of Medicine, School of Medicine (R.L., T.K.H.), Department of Bioengineering (T.B., N.J., F.Y., W.T., H.C., J.L., T.K.H.), and Department of Molecular, Cell, and Developmental Biology (K.W., H.S., J.C.), University of California, Los Angeles; Department of Surgery, Children's Hospital Los Angeles, CA (M.H., C.-L.L.); and Division of Cardiology, Department of Medicine, School of Medicine (H.Y., P.H., N.C.C.) and Institute of Genomic Medicine (N.C.C.), University of California, San Diego, La Jolla.
Tyler BeebeFrom the Department of Medicine, School of Medicine (R.L., T.K.H.), Department of Bioengineering (T.B., N.J., F.Y., W.T., H.C., J.L., T.K.H.), and Department of Molecular, Cell, and Developmental Biology (K.W., H.S., J.C.), University of California, Los Angeles; Department of Surgery, Children's Hospital Los Angeles, CA (M.H., C.-L.L.); and Division of Cardiology, Department of Medicine, School of Medicine (H.Y., P.H., N.C.C.) and Institute of Genomic Medicine (N.C.C.), University of California, San Diego, La Jolla.
Nelson JenFrom the Department of Medicine, School of Medicine (R.L., T.K.H.), Department of Bioengineering (T.B., N.J., F.Y., W.T., H.C., J.L., T.K.H.), and Department of Molecular, Cell, and Developmental Biology (K.W., H.S., J.C.), University of California, Los Angeles; Department of Surgery, Children's Hospital Los Angeles, CA (M.H., C.-L.L.); and Division of Cardiology, Department of Medicine, School of Medicine (H.Y., P.H., N.C.C.) and Institute of Genomic Medicine (N.C.C.), University of California, San Diego, La Jolla.
Fei YuFrom the Department of Medicine, School of Medicine (R.L., T.K.H.), Department of Bioengineering (T.B., N.J., F.Y., W.T., H.C., J.L., T.K.H.), and Department of Molecular, Cell, and Developmental Biology (K.W., H.S., J.C.), University of California, Los Angeles; Department of Surgery, Children's Hospital Los Angeles, CA (M.H., C.-L.L.); and Division of Cardiology, Department of Medicine, School of Medicine (H.Y., P.H., N.C.C.) and Institute of Genomic Medicine (N.C.C.), University of California, San Diego, La Jolla.
Wakako TakabeFrom the Department of Medicine, School of Medicine (R.L., T.K.H.), Department of Bioengineering (T.B., N.J., F.Y., W.T., H.C., J.L., T.K.H.), and Department of Molecular, Cell, and Developmental Biology (K.W., H.S., J.C.), University of California, Los Angeles; Department of Surgery, Children's Hospital Los Angeles, CA (M.H., C.-L.L.); and Division of Cardiology, Department of Medicine, School of Medicine (H.Y., P.H., N.C.C.) and Institute of Genomic Medicine (N.C.C.), University of California, San Diego, La Jolla.
Michael HarrisonFrom the Department of Medicine, School of Medicine (R.L., T.K.H.), Department of Bioengineering (T.B., N.J., F.Y., W.T., H.C., J.L., T.K.H.), and Department of Molecular, Cell, and Developmental Biology (K.W., H.S., J.C.), University of California, Los Angeles; Department of Surgery, Children's Hospital Los Angeles, CA (M.H., C.-L.L.); and Division of Cardiology, Department of Medicine, School of Medicine (H.Y., P.H., N.C.C.) and Institute of Genomic Medicine (N.C.C.), University of California, San Diego, La Jolla.
Hung CaoFrom the Department of Medicine, School of Medicine (R.L., T.K.H.), Department of Bioengineering (T.B., N.J., F.Y., W.T., H.C., J.L., T.K.H.), and Department of Molecular, Cell, and Developmental Biology (K.W., H.S., J.C.), University of California, Los Angeles; Department of Surgery, Children's Hospital Los Angeles, CA (M.H., C.-L.L.); and Division of Cardiology, Department of Medicine, School of Medicine (H.Y., P.H., N.C.C.) and Institute of Genomic Medicine (N.C.C.), University of California, San Diego, La Jolla.
Juhyun LeeFrom the Department of Medicine, School of Medicine (R.L., T.K.H.), Department of Bioengineering (T.B., N.J., F.Y., W.T., H.C., J.L., T.K.H.), and Department of Molecular, Cell, and Developmental Biology (K.W., H.S., J.C.), University of California, Los Angeles; Department of Surgery, Children's Hospital Los Angeles, CA (M.H., C.-L.L.); and Division of Cardiology, Department of Medicine, School of Medicine (H.Y., P.H., N.C.C.) and Institute of Genomic Medicine (N.C.C.), University of California, San Diego, La Jolla.
Hongbo YangFrom the Department of Medicine, School of Medicine (R.L., T.K.H.), Department of Bioengineering (T.B., N.J., F.Y., W.T., H.C., J.L., T.K.H.), and Department of Molecular, Cell, and Developmental Biology (K.W., H.S., J.C.), University of California, Los Angeles; Department of Surgery, Children's Hospital Los Angeles, CA (M.H., C.-L.L.); and Division of Cardiology, Department of Medicine, School of Medicine (H.Y., P.H., N.C.C.) and Institute of Genomic Medicine (N.C.C.), University of California, San Diego, La Jolla.
Peidong HanFrom the Department of Medicine, School of Medicine (R.L., T.K.H.), Department of Bioengineering (T.B., N.J., F.Y., W.T., H.C., J.L., T.K.H.), and Department of Molecular, Cell, and Developmental Biology (K.W., H.S., J.C.), University of California, Los Angeles; Department of Surgery, Children's Hospital Los Angeles, CA (M.H., C.-L.L.); and Division of Cardiology, Department of Medicine, School of Medicine (H.Y., P.H., N.C.C.) and Institute of Genomic Medicine (N.C.C.), University of California, San Diego, La Jolla.
Kevin WangFrom the Department of Medicine, School of Medicine (R.L., T.K.H.), Department of Bioengineering (T.B., N.J., F.Y., W.T., H.C., J.L., T.K.H.), and Department of Molecular, Cell, and Developmental Biology (K.W., H.S., J.C.), University of California, Los Angeles; Department of Surgery, Children's Hospital Los Angeles, CA (M.H., C.-L.L.); and Division of Cardiology, Department of Medicine, School of Medicine (H.Y., P.H., N.C.C.) and Institute of Genomic Medicine (N.C.C.), University of California, San Diego, La Jolla.
Hirohito ShimizuFrom the Department of Medicine, School of Medicine (R.L., T.K.H.), Department of Bioengineering (T.B., N.J., F.Y., W.T., H.C., J.L., T.K.H.), and Department of Molecular, Cell, and Developmental Biology (K.W., H.S., J.C.), University of California, Los Angeles; Department of Surgery, Children's Hospital Los Angeles, CA (M.H., C.-L.L.); and Division of Cardiology, Department of Medicine, School of Medicine (H.Y., P.H., N.C.C.) and Institute of Genomic Medicine (N.C.C.), University of California, San Diego, La Jolla.
Jaunian ChenFrom the Department of Medicine, School of Medicine (R.L., T.K.H.), Department of Bioengineering (T.B., N.J., F.Y., W.T., H.C., J.L., T.K.H.), and Department of Molecular, Cell, and Developmental Biology (K.W., H.S., J.C.), University of California, Los Angeles; Department of Surgery, Children's Hospital Los Angeles, CA (M.H., C.-L.L.); and Division of Cardiology, Department of Medicine, School of Medicine (H.Y., P.H., N.C.C.) and Institute of Genomic Medicine (N.C.C.), University of California, San Diego, La Jolla.
Ching-Ling LienFrom the Department of Medicine, School of Medicine (R.L., T.K.H.), Department of Bioengineering (T.B., N.J., F.Y., W.T., H.C., J.L., T.K.H.), and Department of Molecular, Cell, and Developmental Biology (K.W., H.S., J.C.), University of California, Los Angeles; Department of Surgery, Children's Hospital Los Angeles, CA (M.H., C.-L.L.); and Division of Cardiology, Department of Medicine, School of Medicine (H.Y., P.H., N.C.C.) and Institute of Genomic Medicine (N.C.C.), University of California, San Diego, La Jolla.
Neil C ChiFrom the Department of Medicine, School of Medicine (R.L., T.K.H.), Department of Bioengineering (T.B., N.J., F.Y., W.T., H.C., J.L., T.K.H.), and Department of Molecular, Cell, and Developmental Biology (K.W., H.S., J.C.), University of California, Los Angeles; Department of Surgery, Children's Hospital Los Angeles, CA (M.H., C.-L.L.); and Division of Cardiology, Department of Medicine, School of Medicine (H.Y., P.H., N.C.C.) and Institute of Genomic Medicine (N.C.C.), University of California, San Diego, La Jolla.
Tzung K HsiaiFrom the Department of Medicine, School of Medicine (R.L., T.K.H.), Department of Bioengineering (T.B., N.J., F.Y., W.T., H.C., J.L., T.K.H.), and Department of Molecular, Cell, and Developmental Biology (K.W., H.S., J.C.), University of California, Los Angeles; Department of Surgery, Children's Hospital Los Angeles, CA (M.H., C.-L.L.); and Division of Cardiology, Department of Medicine, School of Medicine (H.Y., P.H., N.C.C.) and Institute of Genomic Medicine (N.C.C.), University of California, San Diego, La Jolla. thsiai@mednet.ucla.edu.
Children's Hospital of Los Angeles · US
Funding
Linking Spatial Variations Shear Stress-Oxidative StressR01HL083015 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HSIAI, TZUNG K · 2006 to 2015
$3.9MElectronica Impedance to Access Metabolically Active PlaqueR01HL118650 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HSIAI, TZUNG K · 2014 to 2022
$3.3MMicro-Sensors to Study Electrical and Mechanical Coupling of Injured MyocardiumR01HL111437 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HSIAI, TZUNG K, XU, XIAOLEI · 2012 to 2020
$3.1MMolecular Mechanisms of Zebrafish Heart RegenerationR01HL096121 · NHLBI · CHILDREN'S HOSPITAL OF LOS ANGELES · PI LIEN, CHING-LING E · 2010 to 2014
$2.0MElectrical Biophysical Forces Impact Cardiac MorphogenesisR01HD069305 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHI, NEIL C · 2011 to 2015
$1.6MElucidating the molecular mechanisms regulating embryonic cardiac rhythmicityR01HL096980 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHEN, JAU-NIAN · 2010 to 2013
$1.5MNHLBI NIH HHS R01 HL083015NHLBI NIH HHS R01HL-083015NHLBI NIH HHS R01 HL096121NHLBI NIH HHS R01HL096121NHLBI NIH HHS R01 HL096980NHLBI NIH HHS R01 HL111437NHLBI NIH HHS R01HL111437NHLBI NIH HHS R01 HL118650NICHD NIH HHS R01 HD069305NICHD NIH HHS R01HD069305
Abstract
objectiveFluid shear stress intimately regulates vasculogenesis and endothelial homeostasis. The canonical Wnt/β-catenin signaling pathways play an important role in differentiation and proliferation. In this study, we investigated whether shear stress activated angiopoietin-2 (Ang-2) via the canonical Wnt signaling pathway with an implication in vascular endothelial repair. APPROACH AND
resultsOscillatory shear stress upregulated both TOPflash Wnt reporter activities and the expression of Ang-2 mRNA and protein in human aortic endothelial cells accompanied by an increase in nuclear β-catenin intensity. Oscillatory shear stress-induced Ang-2 and Axin-2 mRNA expression was downregulated in the presence of a Wnt inhibitor, IWR-1, but was upregulated in the presence of a Wnt agonist, LiCl. Ang-2 expression was further downregulated in response to a Wnt signaling inhibitor, DKK-1, but was upregulated by Wnt agonist Wnt3a. Both DKK-1 and Ang-2 siRNA inhibited endothelial cell migration and tube formation, which were rescued by human recombinant Ang-2. Both Ang-2 and Axin-2 mRNA downregulation was recapitulated in the heat-shock-inducible transgenic Tg(hsp70l:dkk1-GFP) zebrafish embryos at 72 hours post fertilization. Ang-2 morpholino injection of Tg (kdrl:GFP) fish impaired subintestinal vessel formation at 72 hours post fertilization, which was rescued by zebrafish Ang-2 mRNA coinjection. Inhibition of Wnt signaling with IWR-1 also downregulated Ang-2 and Axin-2 expression and impaired vascular repair after tail amputation, which was rescued by zebrafish Ang-2 mRNA injection.
conclusionsShear stress activated Ang-2 via canonical Wnt signaling in vascular endothelial cells, and Wnt-Ang-2 signaling is recapitulated in zebrafish embryos with a translational implication in vascular development and repair.
Indexed as
Mechanotransduction, CellularNeovascularization, PhysiologicWnt Signaling PathwayAngiopoietin-2AnimalsAnimals, Genetically ModifiedAxin ProteinCell MovementCell ProliferationCells, CulturedGene Expression Regulation, DevelopmentalGenes, ReporterGreen Fluorescent ProteinsHumansHuman Umbilical Vein Endothelial CellsIntercellular Signaling Peptides and ProteinsAngiopoietin-2ANGPT2 protein, humanAxin Proteindkk1b protein, zebrafishDKK1 protein, humanGreen Fluorescent ProteinsIntercellular Signaling Peptides and ProteinsRNA, MessengerWnt3A ProteinWNT3A protein, humanZebrafish Proteinsangiopoietin-2DKK-1/dickkopfs-1endothelial repairshuman aortic endothelial cells (HAEC)vasculogenesisWnt signalingzebrafish
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