title: CD146 short isoform increases the proangiogenic potential of endothelial progenitor cells in vitro and in vivo.
abstract: BACKGROUND
  CD146, a transmembrane immunoglobulin mainly expressed at the intercellular junction of endothelial cells, is involved in cell-cell cohesion, paracellular permeability, monocyte transmigration and angiogenesis. CD146 exists as 2 isoforms, short (sh) and long (lg), but which isoform is involved remains undefined.
  
  
  OBJECTIVE
  The recently described role of CD146 in angiogenesis prompted us to investigate which isoform was involved in this process in human late endothelial progenitors (EPCs), with the objective of increasing their proangiogenic potential.
  
  
  RESULTS
  Immunofluorescence experiments showed that, in subconfluent EPCs, shCD146 was localized in the nucleus and at the migrating edges of the membrane, whereas lgCD146 was intracellular. In confluent cells, shCD146 was redistributed at the apical membrane and lgCD146 was directed toward the junction. In contrast to lgCD146, shCD146 was overexpressed in EPCs as compared to mature endothelial cells and upregulated by vascular endothelial growth factor and SDF-1 (stromal cell-derived factor 1). Study of the properties of both isoforms in vitro provided evidence that shCD146 was involved in EPC adhesion to activated endothelium, migration, and proliferation, with a paracrine secretion of interleukin-8 or angiopoietin 2, whereas lgCD146 was implicated in stabilization of capillary-like structures in Matrigel and transendothelial permeability. In an animal model of hindlimb ischemia, transplantation of shCD146-modified EPCs selectively promoted both EPC engraftment and blood flow.
  
  
  CONCLUSIONS
  Altogether, these findings establish that CD146 isoforms display distinct functions in vessels regeneration. Selective improvement of therapeutic angiogenesis by shCD146 overexpression suggests a potential interest of shCD146-transduced EPCs for the treatment of peripheral ischemic disease.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale UMR-S 608, Physiopathologie de l'Endothélium, Université de la Méditerranée, UFR Pharmacie, Marseille, France.
authors.forename: Abdeldjalil
authors.initials: A
authors.lastname: Kebir
authors.forename: Karim
authors.initials: K
authors.lastname: Harhouri
authors.forename: Benjamin
authors.initials: B
authors.lastname: Guillet
authors.forename: Jia Wei
authors.initials: JW
authors.lastname: Liu
authors.forename: Alexandrine
authors.initials: A
authors.lastname: Foucault-Bertaud
authors.forename: Edouard
authors.initials: E
authors.lastname: Lamy
authors.forename: Elise
authors.initials: E
authors.lastname: Kaspi
authors.forename: Nadia
authors.initials: N
authors.lastname: Elganfoud
authors.forename: Frédéric
authors.initials: F
authors.lastname: Vely
authors.forename: Florence
authors.initials: F
authors.lastname: Sabatier
authors.forename: José
authors.initials: J
authors.lastname: Sampol
authors.forename: Pascale
authors.initials: P
authors.lastname: Pisano
authors.forename: Egbert K O
authors.initials: EK
authors.lastname: Kruithof
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bardin
authors.forename: Françoise
authors.initials: F
authors.lastname: Dignat-George
authors.forename: Marcel
authors.initials: M
authors.lastname: Blot-Chabaud
mesh_terms: D000818:Animals; D051929:CD146 Antigen / Q000096:biosynthesis / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology* / Q000637:transplantation; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000502:physiology; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000502:physiology*
chemical_list: D051929:CD146 Antigen; D020033:Protein Isoforms