title: In vivo modulation of endothelial polarization by Apelin receptor signalling.
abstract: Endothelial cells (ECs) respond to shear stress by aligning in the direction of flow. However, how ECs respond to flow in complex in vivo environments is less clear. Here we describe an endothelial-specific transgenic zebrafish line, whereby the Golgi apparatus is labelled to allow for in vivo analysis of endothelial polarization. We find that most ECs polarize within 4.5 h after the onset of vigorous blood flow and, by manipulating cardiac function, observe that flow-induced EC polarization is a dynamic and reversible process. Based on its role in EC migration, we analyse the role of Apelin signalling in EC polarization and find that it is critical for this process. Knocking down Apelin receptor function in human primary ECs also affects their polarization. Our study provides new tools to analyse the mechanisms of EC polarization in vivo and reveals an important role in this process for a signalling pathway implicated in cardiovascular disease.
authors.affiliation: Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany.
authors.forename: Hyouk-Bum
authors.initials: HB
authors.lastname: Kwon
authors.affiliation: Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Ludwigstraße 43, 61231 Bad Nauheim, Germany.
authors.forename: Shengpeng
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany.
authors.forename: Christian S M
authors.initials: CS
authors.lastname: Helker
authors.affiliation: Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany.
authors.forename: S Javad
authors.initials: SJ
authors.lastname: Rasouli
authors.affiliation: Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany.
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Maischein
authors.affiliation: Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Ludwigstraße 43, 61231 Bad Nauheim, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Offermanns
authors.affiliation: University of Münster, Schlossplatz 2, 48149 Münster, Germany.|Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Herzog
authors.affiliation: Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany.
authors.forename: Didier Y R
authors.initials: DY
authors.lastname: Stainier
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000073861:Apelin / Q000235:genetics* / Q000378:metabolism; D000075244:Apelin Receptors / Q000235:genetics* / Q000378:metabolism; D001696:Biomechanical Phenomena; D002465:Cell Movement; D016764:Cell Polarity; D018925:Chemokines / Q000235:genetics* / Q000378:metabolism; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D006056:Golgi Apparatus / Q000378:metabolism; D018056:Hemorheology; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007814:Larva / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D015398:Signal Transduction; D013314:Stress, Mechanical; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C115436:APLN protein, human; C104575:APLNR protein, human; D000073861:Apelin; D000075244:Apelin Receptors; D018925:Chemokines; D029961:Zebrafish Proteins; C519093:apelin receptor, zebrafish; C519092:apln protein, zebrafish