| Endothelial dysfunction, the earliest step in the process of atherosclerosis, is present in obese children. Exercise and/or a change of diet improve endothelial dysfunction at the macrovascular level in as little as 6 to 8 weeks. Yet, growing evidence suggests that endothelial dysfunction develops independently at the macro- and microvascular level and the reversibility of microvascular endothelial dysfunction was not investigated.;Therefore, we aimed to further characterize the impact of obesity on microvascular function in young children. In addition we wanted to determine whether combining diet and exercise, reverses abnormalities in microvascular function.;In a first study, we confirmed that obese children have microvascular endothelial dysfunction, but also fewer Endothelial Progenitor Cells (EPC) and more Endothelial MicroParticles (EMP) compared to normal-weight children. These factors turned out to be independent determinants of microvascular endothelial dysfunction on multiple regression analysis.;We demonstrated that microvascular endothelial dysfunction in obese children can be reversed to values comparable in normal-weight children after a treatment program of supervised diet and exercise training, after completion of the entire 10-month program. This indicates that prolonged treatment is required. The program induced a biphasic response of EPC and EMP, with an initial significant increase in circulating EPC at 5 months, followed by a marked reduction in EMP at 10 months.;Finally, we provide the first preliminary evidence that Circulating Angiogenic Cells (CAC) from obese children are functionally impaired but, in contrast to CAC from obese adults, not yet resistant to the pro-angiogenic actions of leptin. As such, CAC dysfunction might be another mechanism underlying defective endothelial repair in childhood obesity.;Taken together, these findings suggest that severe childhood obesity results in vascular endothelial damage along with reduced capacity to repair the endothelium. Nonetheless, long-term commitment to programs combining exercise a moderately restrictive diet seems to represent an optimal strategy to restore microvascular endothelial function and damage to normal in this population. Further research is necessary to better understand the basic mechanisms that predispose obese children to develop endothelial dysfunction, not only for academic reasons but more importantly to safeguard the cardiovascular future of our society's obese children. |
