title: Adiponectin pretreatment counteracts the detrimental effect of a diabetic environment on endothelial progenitors.
abstract: OBJECTIVE
  It has been shown that vascular progenitors from patients with diabetes are dysfunctional. However, therapeutic strategies to counteract their reduced functional capacity are still lacking. Because adiponectin has reported salutary effects on endothelial function, we investigated the functional effects of globular adiponectin (gAcrp), the active domain of adiponectin, on isolated endothelial colony-forming cells (ECFC).
  
  
  METHODS
  ECFC were isolated from peripheral blood of type 2 diabetic patients (dmECFC) and compared with ECFC of healthy young volunteers (yECFC) and nondiabetic age-matched control subjects (hECFC). Cells were treated with gAcrp for 48 h followed by assessment of cell counts, cell cycle analysis, and migration capacity. For in vivo evaluation, human ECFC were injected into normoglycemic or streptozotocin-induced hyperglycemic nu/nu mice after hind limb ischemia.
  
  
  RESULTS
  Whereas dmECFC were functionally impaired compared with yECFC and hECFC, gAcrp significantly enhanced their in vitro proliferation and migratory activity. In vitro effects were significantly stronger in hECFC compared with dmECFC and were mediated through the cyclooxygenase-2 pathway. Most important, however, we observed a profound and sustained increase of the in vivo neovascularization in mice receiving gAcrp-pretreated dmECFC compared with untreated dmECFC under both normoglycemic and hyperglycemic conditions.
  
  
  CONCLUSIONS
  Pretreatment of ECFC with gAcrp enhanced the functional capacity of ECFC in vitro and in vivo in normoglycemic and hyperglycemic environments. Therefore, preconditioning of dmECFC with gAcrp may be a novel approach to counteract their functional impairment in diabetes.
authors.affiliation: Clinical Research Programme, Spanish National Cancer Research Centre, Madrid, Spain.
authors.forename: Simon F
authors.initials: SF
authors.lastname: Leicht
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Schwarz
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Hermann
authors.forename: Jochen
authors.initials: J
authors.lastname: Seissler
authors.forename: Alexandra
authors.initials: A
authors.lastname: Aicher
authors.forename: Christopher
authors.initials: C
authors.lastname: Heeschen
mesh_terms: D052242:Adiponectin / Q000378:metabolism / Q000494:pharmacology*; D000368:Aged; D000818:Animals; D002452:Cell Count; D002453:Cell Cycle; D016009:Chi-Square Distribution; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D007511:Ischemia / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D018709:Statistics, Nonparametric
chemical_list: D052242:Adiponectin; D051546:Cyclooxygenase 2