title: Thrombospondin-1 is a plasmatic marker of peripheral arterial disease that modulates endothelial progenitor cell angiogenic properties.
abstract: OBJECTIVE
  We examined whether plasma levels of angiogenic factors are altered in plasma of patients with peripheral arterial disease (PAD) and whether these factors affect endothelial progenitor cell-induced angiogenesis.
  
  
  RESULTS
  Plasma was collected from 184 patients with PAD and 330 age-matched healthy controls. Vascular endothelial growth factor and placental growth factor concentrations did not differ between the groups, whereas we found a linear correlation between PAD disease and thrombospondin (TSP)-1 plasma level. TSP-1 was expressed in newly formed vessels in PAD patients having received local injections of bone marrow mononuclear cells. To analyze the functional role of TSP-1 during neoangiogenesis, we used a Matrigel-plug assay and showed that vascularization of implanted Matrigel-plugs was increased in TSP-1(-/-) mice. Moreover, injections of TSP-1 in C57Bl6/J mice after hindlimb ischemia induced a significant decrease of blood flow recovery. To investigate the effects of TSP-1 on human endothelial colony-forming cell (ECFC) angiogenic potential, recombinant human TSP-1 and a small interfering RNA were used. In vitro, TSP-1 N-terminal part significantly enhanced ECFC adhesion, whereas recombinant human TSP-1 had a negative effect on ECFC angiogenic potential. This effect, mediated by CD47 binding, modulated stromal cell-derived factor 1/CXC chemokine receptor 4 pathway.
  
  
  CONCLUSIONS
  TSP-1 is a potential biomarker of PAD and ECFC-induced angiogenesis, suggesting that TSP-1 modulation might improve local tissue ischemia in this setting. (
  
  
  BACKGROUND
  NCT00377897.).
authors.affiliation: Université Paris Descartes, Paris, France. david.smadja@egp.aphp.fr
authors.forename: David M
authors.initials: DM
authors.lastname: Smadja
authors.forename: Clément
authors.initials: C
authors.lastname: d'Audigier
authors.forename: Ivan
authors.initials: I
authors.lastname: Bièche
authors.forename: Solène
authors.initials: S
authors.lastname: Evrard
authors.forename: Laetitia
authors.initials: L
authors.lastname: Mauge
authors.forename: Juliana-Vieira
authors.initials: JV
authors.lastname: Dias
authors.forename: Julien
authors.initials: J
authors.lastname: Labreuche
authors.forename: Ingrid
authors.initials: I
authors.lastname: Laurendeau
authors.forename: Bérengère
authors.initials: B
authors.lastname: Marsac
authors.forename: Blandine
authors.initials: B
authors.lastname: Dizier
authors.forename: Orianne
authors.initials: O
authors.lastname: Wagner-Ballon
authors.forename: Catherine
authors.initials: C
authors.lastname: Boisson-Vidal
authors.forename: Verônica
authors.initials: V
authors.lastname: Morandi
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Duong-Van-Huyen
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
authors.forename: Françoise
authors.initials: F
authors.lastname: Dignat-George
authors.forename: Joseph
authors.initials: J
authors.lastname: Emmerich
authors.forename: Pascale
authors.initials: P
authors.lastname: Gaussem
mesh_terms: D042501:Angiogenic Proteins / Q000008:administration & dosage / Q000097:blood* / Q000172:deficiency / Q000235:genetics; D000818:Animals; D015415:Biomarkers / Q000097:blood; D051928:CD47 Antigen / Q000378:metabolism; D016022:Case-Control Studies; D002448:Cell Adhesion; D049109:Cell Proliferation; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism* / Q000637:transplantation; D006614:Hindlimb; D006801:Humans; D007511:Ischemia / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000098:blood supply*; D018919:Neovascularization, Physiologic; D058729:Peripheral Arterial Disease / Q000097:blood* / Q000503:physiopathology / Q000601:surgery; D010641:Phenotype; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000097:blood; D034622:RNA Interference; D019718:Receptors, CXCR4 / Q000378:metabolism; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*; D019700:Thrombospondin 1 / Q000008:administration & dosage / Q000097:blood* / Q000172:deficiency / Q000235:genetics; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D042501:Angiogenic Proteins; D015415:Biomarkers; D051928:CD47 Antigen; D054377:Chemokine CXCL12; C000608036:PGF protein, human; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D019718:Receptors, CXCR4; D019700:Thrombospondin 1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor