title: Pleiotrophin promotes capillary-like sprouting from senescent aortic rings.
abstract: BACKGROUND
  Pleiotrophin (PTN) is a heparin-binding growth factor involved in angiogenesis during development and tumor growth. Plasmid therapy with PTN also induces angiogenesis after myocardial infarction. During aging, angiogenesis is impaired and we therefore examined whether a growth factor therapy with PTN is able to restore neovascularization.
  
  
  METHODS
  We evaluated the PTN effects on capillary-like endothelial sprouting in adult (n = 10) and senescent (n = 10) rats, using an ex vivo model of explanted aortic segments in culture. Freshly cut thoracic aortic rings from 3 and 24 month old (mo) rats (both n = 12) were cultured in a 3-dimensional collagen matrix with or without addition of recombinant human PTN (2.5-250 ng/ml) or Vascular Endothelial Growth Factor-165 (VEGF) (1-100 ng/ml) and the length of developed capillary network was quantified at day 3 and 6 by image analysis.
  
  
  RESULTS
  After 6 days of culture, capillary-like tube formation was lower in control conditions in 24 mo aortic rings than in 3 mo rings. Addition of PTN increased dose-dependently the length of capillary-like tube formation in both 3 and 24 mo rings (P < 0.001 and P < 0.001 respectively). Age-associated impairment of capillary-like tube formation had been successfully restored in senescent aortic segments by PTN treatment. PTN induced development of capillary network similar to that observed with VEGF therapy with doses equal or superior to 10 ng/ml.
  
  
  CONCLUSIONS
  PTN is able to induce ex vivo angiogenesis during aging and might be a new promising therapy to induce neovascularization in aged tissues as well as after age-associated cardiac, hindlimb or cerebral ischemia.
authors.affiliation: Laboratoire Croissance Cellulaire, Réparation et Régénération Tissulaires, EAC CNRS 7149, Université Paris-Est, Créteil, France. Sophie.Besse@parisdescartes.fr
authors.forename: Sophie
authors.initials: S
authors.lastname: Besse
authors.forename: Romain
authors.initials: R
authors.lastname: Comte
authors.forename: Sophie
authors.initials: S
authors.lastname: Fréchault
authors.forename: José
authors.initials: J
authors.lastname: Courty
authors.forename: de Leiris
authors.initials: de L
authors.lastname: Joël
authors.forename: Jean
authors.initials: J
authors.lastname: Delbé
mesh_terms: D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology*; D002352:Carrier Proteins / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C066845:pleiotrophin