CD146 short isoform increases the proangiogenic potential of endothelial progenitor cells in vitro and in vivo

Article Article scientifique Revue de la littérature CD146 short isoform increases the proangiogenic potential of endothelial progenitor cells in vitro and in vivo eng 2010 author Kebir Abdeldjalil author Harhouri Karim author Guillet Benjamin author Liu Jia Wei 56659 author Foucault-Bertaud Alexandrine author Lamy Edouard author Kaspi Elise author Elganfoud Nadia author Vely Frederic author Sabatier Florence author Sampol Jose author Pisano Pascale author Kruithof Egbert 117791 author Bardin Nathalie Jenny Louise 38429 author Dignat-George Francoise author Blot-Chabaud Marcel 66-75 10.1161/CIRCRESAHA.109.213827 20448216 0009-7330 RATIONALE: 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. METHODS AND 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. Animals Antigens, CD146/biosynthesis/*physiology Endothelium, Vascular/*cytology/*physiology/transplantation Hindlimb/blood supply Humans Ischemia/metabolism/pathology/surgery Mice Neovascularization, Physiologic/*physiology Protein Isoforms/biosynthesis/physiology Stem Cell Transplantation/methods Stem Cells/*physiology Dewey 616 56 Département de médecine 221 false 9 Endothélium vasculaire 11 Circulation research 107 1 13688a9f-d507-4590-a1f8-7d370d806b8d Article Restricted file1.pdf 2066529 application/pdf restrictedAccess Faculté de médecine / Section de médecine clinique / Département de médecine

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CD146 short isoform increases the proangiogenic potential of endothelial progenitor cells in vitro and in vivo	Circulation research			2010	656	0

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Bardin, Nathalie Jenny Louise