title: Sympathetic Innervation Promotes Arterial Fate by Enhancing Endothelial ERK Activity.
abstract: BACKGROUND
  Arterial endothelial cells are morphologically, functionally, and molecularly distinct from those found in veins and lymphatic vessels. How arterial fate is acquired during development and maintained in adult vessels is incompletely understood.
  
  
  OBJECTIVE
  We set out to identify factors that promote arterial endothelial cell fate in vivo.
  
  
  RESULTS
  We developed a functional assay, allowing us to monitor and manipulate arterial fate in vivo, using arteries isolated from quails that are grafted into the coelom of chick embryos. Endothelial cells migrate out from the grafted artery, and their colonization of host arteries and veins is quantified. Here we show that sympathetic innervation promotes arterial endothelial cell fate in vivo. Removal of sympathetic nerves decreases arterial fate and leads to colonization of veins, whereas exposure to sympathetic nerves or norepinephrine imposes arterial fate. Mechanistically, sympathetic nerves increase endothelial ERK (extracellular signal-regulated kinase) activity via adrenergic α1 and α2 receptors.
  
  
  CONCLUSIONS
  These findings show that sympathetic innervation promotes arterial endothelial fate and may lead to novel approaches to improve arterialization in human disease.
authors.affiliation: From the INSERM U970, Paris Center for Cardiovascular Research (PARCC), Paris, France (L.P., L.P.-F., T.M., A.E.); Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT (A.D., M.S., A.E.); and INSERM U1050, Collège de France, Centre Interdisciplinaire de Recherche en Biologie (CIRB), Paris, France (I.E., I.B.). luc.pardanaud@inserm.fr anne.eichmann@inserm.fr.
authors.forename: Luc
authors.initials: L
authors.lastname: Pardanaud
authors.affiliation: From the INSERM U970, Paris Center for Cardiovascular Research (PARCC), Paris, France (L.P., L.P.-F., T.M., A.E.); Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT (A.D., M.S., A.E.); and INSERM U1050, Collège de France, Centre Interdisciplinaire de Recherche en Biologie (CIRB), Paris, France (I.E., I.B.).
authors.forename: Laurence
authors.initials: L
authors.lastname: Pibouin-Fragner
authors.affiliation: From the INSERM U970, Paris Center for Cardiovascular Research (PARCC), Paris, France (L.P., L.P.-F., T.M., A.E.); Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT (A.D., M.S., A.E.); and INSERM U1050, Collège de France, Centre Interdisciplinaire de Recherche en Biologie (CIRB), Paris, France (I.E., I.B.).
authors.forename: Alexandre
authors.initials: A
authors.lastname: Dubrac
authors.affiliation: From the INSERM U970, Paris Center for Cardiovascular Research (PARCC), Paris, France (L.P., L.P.-F., T.M., A.E.); Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT (A.D., M.S., A.E.); and INSERM U1050, Collège de France, Centre Interdisciplinaire de Recherche en Biologie (CIRB), Paris, France (I.E., I.B.).
authors.forename: Thomas
authors.initials: T
authors.lastname: Mathivet
authors.affiliation: From the INSERM U970, Paris Center for Cardiovascular Research (PARCC), Paris, France (L.P., L.P.-F., T.M., A.E.); Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT (A.D., M.S., A.E.); and INSERM U1050, Collège de France, Centre Interdisciplinaire de Recherche en Biologie (CIRB), Paris, France (I.E., I.B.).
authors.forename: Isabel
authors.initials: I
authors.lastname: English
authors.affiliation: From the INSERM U970, Paris Center for Cardiovascular Research (PARCC), Paris, France (L.P., L.P.-F., T.M., A.E.); Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT (A.D., M.S., A.E.); and INSERM U1050, Collège de France, Centre Interdisciplinaire de Recherche en Biologie (CIRB), Paris, France (I.E., I.B.).
authors.forename: Isabelle
authors.initials: I
authors.lastname: Brunet
authors.affiliation: From the INSERM U970, Paris Center for Cardiovascular Research (PARCC), Paris, France (L.P., L.P.-F., T.M., A.E.); Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT (A.D., M.S., A.E.); and INSERM U1050, Collège de France, Centre Interdisciplinaire de Recherche en Biologie (CIRB), Paris, France (I.E., I.B.).
authors.forename: Michael
authors.initials: M
authors.lastname: Simons
authors.affiliation: From the INSERM U970, Paris Center for Cardiovascular Research (PARCC), Paris, France (L.P., L.P.-F., T.M., A.E.); Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT (A.D., M.S., A.E.); and INSERM U1050, Collège de France, Centre Interdisciplinaire de Recherche en Biologie (CIRB), Paris, France (I.E., I.B.). luc.pardanaud@inserm.fr anne.eichmann@inserm.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Eichmann
mesh_terms: D000320:Adrenergic Fibers / Q000201:enzymology*; D000818:Animals; D001158:Arteries / Q000201:enzymology* / Q000254:growth & development / Q000294:innervation*; D002465:Cell Movement / Q000502:physiology; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000201:enzymology / Q000254:growth & development / Q000294:innervation; D003370:Coturnix; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000254:growth & development / Q000294:innervation*; D004789:Enzyme Activation / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000201:enzymology; D006801:Humans; D009924:Organ Culture Techniques; D017933:Peripheral Nervous System / Q000201:enzymology / Q000254:growth & development; D016378:Tissue Transplantation / Q000379:methods; D014469:Umbilical Arteries / Q000201:enzymology / Q000254:growth & development
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases
keywords: ERK; VEGF signaling; arterial–venous endothelial differentiation; embryonic development; sympathetic nervous system