title: PPARγ activation but not PPARγ haplodeficiency affects proangiogenic potential of endothelial cells and bone marrow-derived progenitors.
abstract: BACKGROUND
  Peroxisome proliferator-activated receptor-γ (PPARγ) agonists, which have been used as insulin sensitizers in diabetic patients, may improve functions of endothelial cells (ECs). We investigated the effect of PPARγ on angiogenic activities of murine ECs and bone marrow-derived proangiogenic cells (PACs).
  
  
  METHODS
  PACs were isolated from bone marrow of 10-12 weeks old, wild type, db/db and PPARγ heterozygous animals. Cells were cultured on fibronectin and gelatin coated dishes in EGM-2MV medium. For in vitro stimulations, rosiglitazone (10 μmol/L) or GW9662 (10 μmol/L) were added to 80% confluent cell cultures for 24 hours. Angiogenic potential of PACs and ECs was tested in vitro and in vivo in wound healing assay and hind limb ischemia model.
  
  
  RESULTS
  ECs and PACs isolated from diabetic db/db mice displayed a reduced angiogenic potential in ex vivo and in vitro assays, the effect partially rescued by incubation of cells with rosiglitazone (PPARγ activator). Correction of diabetes by administration of rosiglitazone in vivo did not improve angiogenic potential of isolated PACs or ECs. In a hind limb ischemia model we demonstrated that local injection of conditioned media harvested from wild type PACs improved the blood flow restoration in db/db mice, confirming the importance of paracrine action of the bone marrow-derived cells.
  
  
  CONCLUSIONS
  In summary, activation of PPARγ by rosiglitazone improves angiogenic potential of diabetic ECs and PACs, but decreased expression of PPARγ in diabetes does not impair angiogenesis.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Kotlinowski
authors.forename: Anna
authors.initials: A
authors.lastname: Grochot-Przeczek
authors.forename: Hevidar
authors.initials: H
authors.lastname: Taha
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kozakowska
authors.forename: Bartosz
authors.initials: B
authors.lastname: Pilecki
authors.forename: Klaudia
authors.initials: K
authors.lastname: Skrzypek
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Bartelik
authors.forename: Rafal
authors.initials: R
authors.lastname: Derlacz
authors.forename: Anton J G
authors.initials: AJ
authors.lastname: Horrevoets
authors.forename: Attila
authors.initials: A
authors.lastname: Pap
authors.forename: Laszlo
authors.initials: L
authors.lastname: Nagy
authors.forename: Jozef
authors.initials: J
authors.lastname: Dulak
authors.forename: Alicja
authors.initials: A
authors.lastname: Jozkowicz
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007511:Ischemia / Q000188:drug therapy; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D000077154:Rosiglitazone; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects
chemical_list: D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone