title: A switch toward angiostatic gene expression impairs the angiogenic properties of endothelial progenitor cells in low birth weight preterm infants.
abstract: Low birth weight (LBW) is associated with increased risk of cardiovascular diseases at adulthood. Nevertheless, the impact of LBW on the endothelium is not clearly established. We investigate whether LBW alters the angiogenic properties of cord blood endothelial colony forming cells (LBW-ECFCs) in 25 preterm neonates compared with 25 term neonates (CT-ECFCs). We observed that LBW decreased the number of colonies formed by ECFCs and delayed the time of appearance of their clonal progeny. LBW dramatically reduced LBW-ECFC capacity to form sprouts and tubes, to migrate and to proliferate in vitro. The angiogenic defect of LBW-ECFCs was confirmed in vivo by their inability to form robust capillary networks in Matrigel plugs injected in nu/nu mice. Gene profile analysis of LBW-ECFCs demonstrated an increased expression of antiangiogenic genes. Among them, thrombospondin 1 (THBS1) was highly expressed at RNA and protein levels in LBW-ECFCs. Silencing THBS1 restored the angiogenic properties of LBW-ECFCs by increasing AKT phosphorylation. The imbalance toward an angiostatic state provide a mechanistic link between LBW and the impaired angiogenic properties of ECFCs and allows the identification of THBS1 as a novel player in LBW-ECFC defect, opening new perspectives for novel deprogramming agents.
authors.affiliation: Inserm, Unité Mixte de Recherche 608, Physiopathologie de l'Endothélium Marseille, Marseille, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ligi
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Simoncini
authors.forename: Edwige
authors.initials: E
authors.lastname: Tellier
authors.forename: Paula Frizera
authors.initials: PF
authors.lastname: Vassallo
authors.forename: Florence
authors.initials: F
authors.lastname: Sabatier
authors.forename: Benjamin
authors.initials: B
authors.lastname: Guillet
authors.forename: Edouard
authors.initials: E
authors.lastname: Lamy
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Sarlon
authors.forename: Cathy
authors.initials: C
authors.lastname: Quemener
authors.forename: Andreas
authors.initials: A
authors.lastname: Bikfalvi
authors.forename: Maxime
authors.initials: M
authors.lastname: Marcelli
authors.forename: Alain
authors.initials: A
authors.lastname: Pascal
authors.forename: Blandine
authors.initials: B
authors.lastname: Dizier
authors.forename: Umberto
authors.initials: U
authors.lastname: Simeoni
authors.forename: Françoise
authors.initials: F
authors.lastname: Dignat-George
authors.forename: Francine
authors.initials: F
authors.lastname: Anfosso
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D020869:Gene Expression Profiling; D006801:Humans; D007230:Infant, Low Birth Weight / Q000097:blood*; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D018919:Neovascularization, Physiologic / Q000235:genetics*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D019700:Thrombospondin 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D019700:Thrombospondin 1; D051057:Proto-Oncogene Proteins c-akt