title: Rosiglitazone via upregulation of Akt/eNOS pathways attenuates dysfunction of endothelial progenitor cells, induced by advanced glycation end products.
abstract: OBJECTIVE
  Advanced glycation end products (AGEs) and endothelial progenitor cells (EPCs) play key roles in pathogenesis of diabetes-related vascular complications. AGEs can induce dysfunction in EPCs. The peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists are widely used in the treatment of type 2 diabetes, and it remains unknown if they could attenuate EPC dysfunction induced by AGEs.
  
  
  METHODS
  EPCs isolated from healthy adults were cultured with various concentrations of AGEs (0, 50, 100 and 200 mg L(-1)) with or without rosiglitazone (10 nM), antibody for the receptors for AGE-human serum albumin (anti-receptor for advanced glycation end products (RAGE); 50 microg mL(-1)), phosphatidylinositol-3-kinase (PI3K) inhibitor (LY294002, 5 microM), nitric oxide (NO) synthase inhibitor (L-N(G)-nitro-arginine methyl ester (L-NAME), 100 microM) or sodium nitroprusside (SNP, 25 microM). Proliferation, apoptosis, cell adhesion, migration and NO production in EPCs were assessed, and expressions of endothelial NO synthase (eNOS) and Akt were determined.
  
  
  RESULTS
  Number, proliferation/migration capacities, eNOS and Akt phosphorylation as well as NO synthesized by EPCs were increased by rosiglitazone and reduced by AGEs. AGEs promoted while rosiglitazone reduced EPC apoptosis. The AGE-induced effects were significantly ameliorated by pre-incubation with rosiglitazone, RAGE antibody and SNP. The beneficial effects of rosiglitazone could be blocked by pretreatment with L-NAME and LY294002.
  
  
  CONCLUSIONS
  The PPARgamma agonist rosiglitazone increased EPC function and attenuated EPC dysfunction induced by AGEs via upregulating the Akt-eNOS signal pathways of EPCs.
authors.affiliation: Department of Cardiology, Second Hospital Affiliated to the Second Military Medical University, Shanghai, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Liang
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Ren
authors.forename: Hongbin
authors.initials: H
authors.lastname: Tan
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: He
authors.forename: Qijun
authors.initials: Q
authors.lastname: Jiang
authors.forename: Jianxiang
authors.initials: J
authors.lastname: Wu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhen
authors.forename: Min
authors.initials: M
authors.lastname: Fan
authors.forename: Zonggui
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000077154:Rosiglitazone; D013234:Stem Cells / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D017127:Glycation End Products, Advanced; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt