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Vimentin regulates Notch signaling strength and arterial remodeling in response to hemodynamic stress.

Title: Vimentin regulates Notch signaling strength and arterial remodeling in response to hemodynamic stress.
Authors: van Engeland NCA; Åbo Akademi University, Faculty of Science and Engineering, Biosciences, Turku, Finland.; Eindhoven University of Technology, Department of Biomedical Engineering, 5600, MB, Eindhoven, The Netherlands.; Suarez Rodriguez F; Åbo Akademi University, Faculty of Science and Engineering, Biosciences, Turku, Finland.; Turku Bioscience, Åbo Akademi University and University of Turku, Turku, Finland.; Rivero-Müller A; Åbo Akademi University, Faculty of Science and Engineering, Biosciences, Turku, Finland.; Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland.; Ristori T; Åbo Akademi University, Faculty of Science and Engineering, Biosciences, Turku, Finland.; Eindhoven University of Technology, Department of Biomedical Engineering, 5600, MB, Eindhoven, The Netherlands.; Institute of Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands.; Duran CL; Department of Molecular & Cellular Medicine, Texas A&M University Health Science Center, College Station, TX, 77843, Texas, USA.; Stassen OMJA; Åbo Akademi University, Faculty of Science and Engineering, Biosciences, Turku, Finland.; Turku Bioscience, Åbo Akademi University and University of Turku, Turku, Finland.; Antfolk D; Åbo Akademi University, Faculty of Science and Engineering, Biosciences, Turku, Finland.; Turku Bioscience, Åbo Akademi University and University of Turku, Turku, Finland.; Driessen RCH; Eindhoven University of Technology, Department of Biomedical Engineering, 5600, MB, Eindhoven, The Netherlands.; Ruohonen S; Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland.; Ruohonen ST; Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland.; Turku Center for Disease Modelling, University of Turku, Turku, Finland.; Nuutinen S; Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland.; Savontaus E; Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland.; Turku Center for Disease Modelling, University of Turku, Turku, Finland.; Loerakker S; Eindhoven University of Technology, Department of Biomedical Engineering, 5600, MB, Eindhoven, The Netherlands.; Institute of Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands.; Bayless KJ; Department of Molecular & Cellular Medicine, Texas A&M University Health Science Center, College Station, TX, 77843, Texas, USA.; Sjöqvist M; Åbo Akademi University, Faculty of Science and Engineering, Biosciences, Turku, Finland.; Turku Bioscience, Åbo Akademi University and University of Turku, Turku, Finland.; Bouten CVC; Eindhoven University of Technology, Department of Biomedical Engineering, 5600, MB, Eindhoven, The Netherlands.; Institute of Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands.; Eriksson JE; Turku Bioscience, Åbo Akademi University and University of Turku, Turku, Finland.; Sahlgren CM; Åbo Akademi University, Faculty of Science and Engineering, Biosciences, Turku, Finland. cecilia.sahlgren@abo.fi.; Eindhoven University of Technology, Department of Biomedical Engineering, 5600, MB, Eindhoven, The Netherlands. cecilia.sahlgren@abo.fi.; Turku Bioscience, Åbo Akademi University and University of Turku, Turku, Finland. cecilia.sahlgren@abo.fi.; Institute of Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands. cecilia.sahlgren@abo.fi.
Source: Scientific reports [Sci Rep] 2019 Aug 27; Vol. 9 (1), pp. 12415. Date of Electronic Publication: 2019 Aug 27.
Publication Type: Journal Article; Research Support, Non-U.S. Gov't
Language: English
Journal Info: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
Imprint Name(s): Original Publication: London : Nature Publishing Group, copyright 2011-
MeSH Terms: Hemodynamics* ; Signal Transduction* ; Stress, Physiological* ; Vascular Remodeling*; Aorta/*metabolism ; Receptors, Notch/*metabolism ; Vimentin/*metabolism; Jagged-1 Protein/genetics ; Jagged-1 Protein/metabolism ; Muscle, Smooth, Vascular/metabolism ; Myocytes, Smooth Muscle/metabolism ; Receptors, Notch/genetics ; Vimentin/genetics ; Animals ; Human Umbilical Vein Endothelial Cells ; Humans ; Mice ; Mice, Knockout ; Transcriptional Activation
Abstract: The intermediate filament (IF) cytoskeleton has been proposed to regulate morphogenic processes by integrating the cell fate signaling machinery with mechanical cues. Signaling between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) through the Notch pathway regulates arterial remodeling in response to changes in blood flow. Here we show that the IF-protein vimentin regulates Notch signaling strength and arterial remodeling in response to hemodynamic forces. Vimentin is important for Notch transactivation by ECs and vimentin knockout mice (VimKO) display disrupted VSMC differentiation and adverse remodeling in aortic explants and in vivo. Shear stress increases Jagged1 levels and Notch activation in a vimentin-dependent manner. Shear stress induces phosphorylation of vimentin at serine 38 and phosphorylated vimentin interacts with Jagged1 and increases Notch activation potential. Reduced Jagged1-Notch transactivation strength disrupts lateral signal induction through the arterial wall leading to adverse remodeling. Taken together we demonstrate that vimentin forms a central part of a mechanochemical transduction pathway that regulates multilayer communication and structural homeostasis of the arterial wall.
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Grant Information: K12 GM102779 United States GM NIGMS NIH HHS
Substance Nomenclature: 0 (Jag1 protein, mouse); 0 (Jagged-1 Protein); 0 (Receptors, Notch); 0 (Vim protein, mouse); 0 (Vimentin)
Entry Date(s): Date Created: 20190829 Date Completed: 20201021 Latest Revision: 20210110
Update Code: 20260130
PubMed Central ID: PMC6712036
DOI: 10.1038/s41598-019-48218-w
PMID: 31455807
Database: MEDLINE

Journal Article; Research Support, Non-U.S. Gov't