A switch toward angiostatic gene expression impairs the angiogenic properties of endothelial progenitor cells in low birth weight preterm infants

• Published in: Blood Vol. 118; no. 6; pp. 1699 - 1709
• Main Authors: Ligi, Isabelle, Simoncini, Stéphanie, Tellier, Edwige, Vassallo, Paula Frizera, Sabatier, Florence, Guillet, Benjamin, Lamy, Edouard, Sarlon, Gabrielle, Quemener, Cathy, Bikfalvi, Andreas, Marcelli, Maxime, Pascal, Alain, Dizier, Blandine, Simeoni, Umberto, Dignat-George, Françoise, Anfosso, Francine
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 11.08.2011; Americain Society of Hematology
• Subjects: Animals; Biological and medical sciences; Blood Vessels - cytology; Blood Vessels - growth & development; Blood Vessels - metabolism; Blotting, Western; Cell Proliferation; Cells, Cultured; Diseases of mother, fetus and pregnancy; Endothelial Cells - cytology; Endothelial Cells - metabolism; Female; Fetal Blood - cytology; Gene Expression Profiling; Gynecology. Andrology. Obstetrics; Hematologic and hematopoietic diseases; Humans; Infant, Low Birth Weight - blood; Infant, Newborn; Infant, Premature - blood; Male; Medical sciences; Mice; Mice, Inbred Strains; Mice, Nude; Neovascularization, Physiologic - genetics; Phosphorylation; Pregnancy. Fetus. Placenta; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Stem Cell Transplantation - methods; Stem Cells - cytology; Stem Cells - metabolism; Thrombospondin 1 - genetics; Thrombospondin 1 - metabolism; Angiogenesis; Newborn diseases; Endothelial cell; Pregnancy disorders; Hematology; Prematurity; Stem cell; Low birth weight; Neovascularization; Gene expression
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2010-12-325142

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.