Reduction of both number and proliferative activity of human endothelial progenitor cells in obesity

Abstract

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) ¼ 48±9, n ¼ 45) compared with lean (23±2, n ¼ 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.500) and CD133 þ /KDR þ (r ¼ À0.282) EPCs. Insulin, leptin, HbA 1c , 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, EPC-CFUs differentiated into OECs that proliferated more slowly when derived from obese compared with lean subjects (obese: 19.9 ± 2.2% vs lean: 30.9 ± 3.2% grown area per week, Po0.01). The reduced proliferation was reflected by decreased (Po0.05, n ¼ 24 for each group) expression of cell-cyclepromoting cyclins and E2F-1, by hypophosphorylation of retinoblastoma protein and by increased (Po0.05, n ¼ 24 for each group) expression of the cell-cycle inhibitor p21 WAFÀ1/Cip1 . Conclusions: Reduced numbers of EPCs along with their premature senescence, as shown in this study, could function as early contributors to the development and progression of vascular dysfunction in obesity.

Cell Therapy and Critical Limb Ischemia: Evidence and Window of Opportunity in Obesity

“…They also reported that, EPCs colony formation was significantly less in the obese and overweight compared with normal weight adults . Another study by Tobler K, et al [67] reported decreased number and premature senescence of EPCs in obese volunteers which could function as early contributors to the development and progression of vascular dysfunction in obesity. In overweight adolescents, the number of CD34-negative EPCs, but not CD34-positive EPCs was reported to be higher which could indicate higher risk for future cardiovascular disease in obese teenagers [68].…”

Markers of an inflammation and angiogenesis in chronic cerebrovascular diseases

“…К настоящему времени установлено, что повы-шение сывороточного уровня таких сигнальных мо-лекул, как СРБ и хемокина -протеина, стимулиру-ющего миграцию макрофагов (MСР-1), достоверно ассоциировано с пожилым возрастом [17]. Ведущи-ми причинами, вызывающими повышение уровней VEGF в кровотоке здорового человека с возрастом, являются провоспалительный цитокиновый сдвиг, оксидантный стресс и ишемия.…”

Endothelial progenitor cells and vascular health: effects of lifestyle’s modifications

“…È stato infatti dimostrato che i pazienti obesi, rispetto ai controlli normopeso esibiscono un ridotto numero ed anche una ridotta funzionalità delle CEP e che questo effetto di riduzione aumenta con l'aumentare dell'indice di massa corporea [37,38].…”