title: Pioglitazone improves in vitro viability and function of endothelial progenitor cells from individuals with impaired glucose tolerance.
abstract: BACKGROUND
  Evidence suggests that the PPARγ-agonist insulin sensitizer pioglitazone, may provide potential beneficial cardiovascular (CV) effects beyond its anti-hyperglycaemic function. A reduced endothelial progenitor cell (EPC) number is associated with impaired glucose tolerance (IGT) or diabetes, conditions characterised by increased CV risk.
  
  
  OBJECTIVE
  To evaluate whether pioglitazone can provide benefit in vitro in EPCs obtained from IGT subjects.
  
  
  METHODS
  Early and late-outgrowth EPCs were obtained from peripheral blood mononuclear cells of 14 IGT subjects. The in vitro effect of pioglitazone (10 µM) with/without PPARγ-antagonist GW9662 (1 µM) was assessed on EPC viability, apoptosis, ability to form tubular-like structures and pro-inflammatory molecule expression.
  
  
  RESULTS
  Pioglitazone increased early and late-outgrowth EPC viability, with negligible effects on apoptosis. The capacity of EPCs to form tubular-like structures was improved by pioglitazone in early (mean increase 28%; p=0.005) and late-outgrowth (mean increase 30%; p=0.037) EPCs. Pioglitazone reduced ICAM-1 and VCAM-1 adhesion molecule expression in both early (p=0.001 and p=0.012 respectively) and late-outgrowth (p=0.047 and p=0.048, respectively) EPCs. Similarly, pioglitazone reduced TNFα gene and protein expression in both early (p=0.034;p=0.022) and late-outgrowth (p=0.026;p=0.017) EPCs compared to control. These effects were prevented by incubation with the PPARγ-antagonist GW9662.
  
  
  CONCLUSIONS
  Pioglitazone exerts beneficial effects in vitro on EPCs isolated from IGT subjects, supporting the potential implication of pioglitazone as a CV protective agents.
authors.affiliation: Cardiology, Department of Experimental and Applied Medicine, University of Brescia, Brescia, Italy. alessandra.deicas@unipr.it
authors.forename: Valentina
authors.initials: V
authors.lastname: Spigoni
authors.forename: Angela
authors.initials: A
authors.lastname: Picconi
authors.forename: Monia
authors.initials: M
authors.lastname: Cito
authors.forename: Valentina
authors.initials: V
authors.lastname: Ridolfi
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bonomini
authors.forename: Chiara
authors.initials: C
authors.lastname: Casali
authors.forename: Ivana
authors.initials: I
authors.lastname: Zavaroni
authors.forename: Luigi
authors.initials: L
authors.lastname: Gnudi
authors.forename: Marco
authors.initials: M
authors.lastname: Metra
authors.forename: Alessandra
authors.initials: A
authors.lastname: Dei Cas
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D018149:Glucose Intolerance / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D000077205:Pioglitazone; D013234:Stem Cells / Q000187:drug effects / Q000473:pathology*; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D015815:Cell Adhesion Molecules; D018925:Chemokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D045162:Thiazolidinediones; D000077205:Pioglitazone