Exp Clin Endocrinol Diabetes 2007; 115 - P02_057
DOI: 10.1055/s-2007-972464

Number and functional activity of human endothelial progenitor cells are reduced in obesity

M Artwohl 1, K Tobler 1, M Wolzt 2, C Maier 1, B Ludvik 1, A Freudenthaler 1, E Nansalmaa 1, D Seidinger 3, S Steiner 3, A Luger 1, S Baumgartner-Parzer 1
  • 1Medical University of Vienna, Department of Internal Medicine III, Division of Endocrinology and Metabolism, Vienna, Austria
  • 2Medical University of Vienna, Department of Clinical Pharmacology, Vienna, Austria
  • 3Medical University of Vienna, Department of Internal Medicine II, Division of Angiology, Vienna, Austria

Objective: Due to the identification of circulating bone marrow-derived endothelial progenitor cells (EPCs), the paradigm that vasculogenesis is restricted to embryogenesis is now contradicted. EPCs importantly participate in new blood vessel formation and vascular repair and represent a surrogate marker for vascular disease.

Recent data in obese, diabetic mice show that angiogenic activity of EPCs was inhibited compared with lean, non-diabetic controls. Additionally, high concentrations of the adipose tissue-derived hormone leptin impair migration and tube formation in cultured human EPCs. Therefore, the present study evaluated the effects of obesity on number and functional activity of human EPCs.

Methods: Using FACS-analyses, EPCs, expressing CD34+/CD133+/KDR+, were quantified from peripheral blood mononuclear cells (PBMCs), isolated from whole blood of obese- (BMI=39±2 [Range: 30–53], n=9) and lean subjects (BMI=23±1 [Range: 19–29], n=14) by density gradient centrifugation. In vitro, EPCs grew out from colony forming units (CFUs) and, as a result of selective culture conditions, differentiated to mature endothelial cells, which were characterized in situ and by FACS-analyses.

Results: Preliminary data indicate that obese subjects had 78% less (p<0.05) CD34+/CD133+/KDR+-EPCs compared with lean volunteers. Culturing 107 PBMCs for one week resulted in 132±49 CFUs from lean controls, whereas only 42±19 CFUs were obtained from obese patients. The endothelial character of outgrown cells was confirmed by expression of CD31/PECAM, CD144/VE-Cadherin, and CD146/S-endo. The proliferative capacity of endothelial cells, differentiated from the EPCs of lean control subjects, was 17.3±5.4% per week, whereas it was only 8.9±3.2% in endothelial cells, differentiated from obese patients' EPCs.

Conclusions: Reduction of the number of circulating endothelial progenitor cells in obese patients and their diminished proliferative capacity, as shown in in vitro experiments, could well contribute to development and progression of vascular dysfunction.