Abstract 3697: Effects of Obesity and Weight Loss on the Functional Properties of Endothelial Progenitor Cells
Studies have shown that cardiovascular risk factors are associated with a reduction of endothelial progenitor cell (EPC) number and functional capacity, but the effects of obesity have not yet been examined. In the present study, EPC were expanded from the mononuclear cell fraction of 26 obese (age, 44.1±12.9 years; BMI, 44.4±10.7 kg/m2) individuals participating in a professional weight reduction program, and compared to those from 12 age-matched lean controls (BMI, 22.4±2.2 kg/m2). Subjects with glucose intolerance or overt diabetes mellitus were excluded. None of the participants had a history of cardiovascular disease. Plasma levels of leptin (51.3±34.9 vs. 7.3±4.5 ng/mL) and C-reactive protein (10±9.6 vs. 1.3±1.3 mg/L) were elevated in obese subjects compared to lean controls (P<0.005 and P<0.004, respectively). After cultivation for 7 days, significantly less acLDL+, lectin+ EPC were obtained from the obese (P=0.02 vs. lean). Furthermore, studies using the matrigel assay revealed that reduced numbers of EPC from obese persons incorporated into tubular structures provided by mature endothelial cells (66±4% vs. lean; P< 0.001). Notably, incubation with conditioned medium from EPC expanded from lean persons did not rescue the impaired function of ‘obese’ EPC. In this regard, flow cytometry analysis revealed reduced expression of VEGF receptor-2 (P=0.0125) and αvβ5 integrins (P<0.002) on EPC from obese compared to lean individuals, with a tendency towards reduced αvβ3 (7.2±2.3 vs. 21.8±7.9%; P=0.082) and β2 integrin (54.0±7.2 vs. 70.5±8.0%; P=0.144) levels. On the other hand, 24 hour-incubation of EPC from lean individuals with the conditioned medium from ‘obese’ EPC significantly reduced the number of EPC adherent to tubular structures (P<0.001), thus raising the possibility that secretion of angiogenic growth factors by EPC also may be impaired in obesity. Finally, 6-month follow-up revealed that successful weight reduction to a BMI below 35 (6 persons) was associated with normalization of integrin expression levels and of the functional properties of EPC in the matrigel assay. Taken together, our findings suggest that obesity is associated with partly reversible functional impairment of EPC which may involve altered integrin expression.