title: A direct comparison of endothelial progenitor cell dysfunction in rat metabolic syndrome and diabetes.
abstract: OBJECTIVE
  Diabetes mellitus (DM) is associated with impairment of endothelial progenitor cells (EPCs), but the effects of metabolic syndrome (MS) on EPCs have been less well characterized. We hypothesized that in the presence of MS, the number and functionality of EPCs would be markedly reduced, and would be similar to DM.
  
  
  METHODS
  Mononuclear cells were isolated from the bone-marrow (BM) and peripheral blood of lean Zucker, obese Zucker, a model of MS, and Zucker diabetic fatty rats. Cultured BM-EPCs underwent in vitro functional testing and the ability of BM-EPCs to promote neovascularization in vivo was assessed in a model of hindlimb ischemia in athymic mice.
  
  
  RESULTS
  While circulating EPC numbers were similarly reduced in both MS and DM rats, BM-derived EPC numbers were less affected. In vitro testing of cultured BM-EPCs from obese Zucker demonstrated a marked reduction in EPC differentiation, a greater propensity to apoptosis, a reduced migratory response and matrigel tubule formation, similar to findings in Zucker diabetic fatty rats. When delivered to the ischemic hindlimb of athymic mice, the recovery of perfusion using both BM-EPCs from obese Zucker and Zucker diabetic fatty rats were diminished, as compared to lean Zuckers.
  
  
  CONCLUSIONS
  In the presence of the MS, BM-derived EPCs develop marked functional impairment, resulting in severely reduced angiogenic capacity in vivo. Similar to DM, EPC dysfunction may play a prominent role in the pathogenesis of vascular complications in the MS, and may potentially limit the use of BM-derived EPCs for therapeutic angiogenesis.
authors.affiliation: Division of Cardiology, Keenan Research Centre in the Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, 6-044 Queen Wing, 30 Bond Street, Toronto, Ontario, Canada M5B 1W8.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kuliszewski
authors.forename: Michael R
authors.initials: MR
authors.lastname: Ward
authors.forename: James W
authors.initials: JW
authors.lastname: Kowalewski
authors.forename: Alexandra H
authors.initials: AH
authors.lastname: Smith
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Stewart
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kutryk
authors.forename: Howard
authors.initials: H
authors.lastname: Leong-Poi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000166:cytology*; D008297:Male; D024821:Metabolic Syndrome / Q000503:physiopathology*; D018919:Neovascularization, Physiologic; D051381:Rats; D011924:Rats, Zucker; D013234:Stem Cells / Q000502:physiology*