Abstract 1562: Endothelial Progenitor Cell Dysfunction in Morbid Obese is Reversible After Rapid and Intense Weight Loss Despite Maintenance of Increased Body Mass Index
Whether the reduced functional properties of endothelial progenitor cells (EPCs) in morbid obesity improve after severe weight loss is still unknown. We evaluated 25 morbid obese subjects (BMI=49±3kg/m2) before and 6 months after bariatric surgery, as compared with 21 healthy lean controls. Circulating EPC number, decreased in morbid subjects vs controls (0.02913±0.0033 vs 0.05063±0.0023 % events; p<.001; measured by flow cytometry), enhanced 59% after weight loss (−36k; p<.001); with final BMI of 36±2kg/m2). Similar results were obtained by fluorescence analysis. Weight loss also improved EPC migratory capacity in vitro (+12±4 cells/high power field vs obese; p=.014). In vivo skeletal muscle neovascularization (immunofluorescence analysis) after 14 days of hindlimb ischemia in nude mice injected with human EPCs showed significant recovery with EPCs collected after weight loss (+50% vs obese EPCs; p=.008). Likewise, the markedly impaired flow-mediated brachial artery vasodilation in morbid obese vs controls (2.6±0.6 vs 7.2±0.8%; p<.001) was significantly improved after weight loss(+3.6%; 95% CI 0.6 to 7%; p=.039), while showing close correlation with EPC number (standardized coefficient (SC)= .556; p<.001). In contrast, carotid intima-media thickness failed to reduce after weight loss. Importantly, decrease in BMI (SC=−.493; p<.001) and hyperinsulinemia (SC=−.408; p=.002) induced by weight loss showed strong correlation with EPC number recovery by multivariate analysis. Multivariate analysis also revealed that plasma levels of CRP decreased (SC=−.567; p=.001), whereas those of adiponectin increased (SC=.473; p=.005)) in direct correlation with EPC migratory activity. Leptin failed to be an independent factor. These novel findings show that lower circulating number and disrupted function of EPCs in morbid obese is a reversible process, even considering that the majority of individuals was still obese after massive weight loss. CRP and adiponectin apparently have a potential role in the recovery EPC process, which occurred in parallel with reversal of endothelial dysfunction.