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International Journal of Obesity (2010) 34, 687700
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ORIGINAL ARTICLE
Reduction of both number and proliferative activity of human endothelial progenitor cells in obesity
K Tobler1, A Freudenthaler1, SM Baumgartner-Parzer1, M Wolzt1,2, B Ludvik1, E Nansalmaa1,3, PJ Nowotny1, D Seidinger4, S Steiner4, A Luger1 and M Artwohl1,5
1Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria; 2Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria; 3School of Biomedicine, Health Science University, Ulaanbaatar, Mongolia; 4Department of Internal Medicine II, Clinical Division of Angiology, Medical University of Vienna, Vienna, Austria and 5Karl Landsteiner Institute for Endocrinology and Metabolism, Hanusch Hospital Vienna, Vienna, Austria
Objective: Circulating endothelial progenitor cells (EPCs), responsible for neoangiogenesis and vascular repair, negatively correlate with vascular dysfunction and atherosclerotic risk factors. Because obesity may have a crucial role in the development of endothelial dysfunction, this study evaluated the number and proliferative activity of circulating human EPCs in obese (body mass index (BMI) 489, n 45) compared with lean (232, n 45) volunteers.
Methods: EPCs were quantified after isolation of peripheral blood mononuclear cells (PBMCs) using fluorescence-activated cell sorting analyses. In addition, plated PBMCs developed colony-forming units (CFUs) from which outgrowth endothelial cells (OECs) sprouted and differentiated into mature endothelial cells. Growth rates were monitored by periodical microscopic evaluation. Cell-cycle protein expression was determined by western blot analyses.
Results: BMI negatively correlated (Po0.01) with the number of CD34/CD133/KDR (r 0.442), CD34/KDR
(r 0.500) and CD133/KDR (r 0.282) EPCs. Insulin, leptin, HbA1c, high-sensitivity C-reactive protein and hypertension,
as well as diminished high-density lipoprotein and apolipoprotein A1, were not only associated with obesity but also with significantly reduced EPC levels. Applying selective culture conditions, EPCCFUs differentiated into OECs that proliferated more slowly when derived from obese compared with lean subjects (obese: 19.92.2% vs lean: 30.93.2% grown area per week, Po0.01). The reduced proliferation was reflected by decreased (Po0.05, n 24 for each group) expression of cell-cycle-
promoting cyclins and E2F-1, by hypophosphorylation of retinoblastoma protein and by increased (Po0.05, n 24 for each
group) expression of the cell-cycle inhibitor p21WAF 1/Cip1.
Conclusions: Reduced numbers of EPCs along with their premature senescence, as shown in this...