Abstract 14322: Improvement of Endothelial Progenitor Cell Number and Function in Obesity and Diabetes With Thymosin Beta-4
Background: Diabetes mellitus and obesity are cardiovascular risk factors which are associated with endothelial dysfunction and atherosclerosis. As mature endothelial cells have limited regenerative capacity, endothelial progenitor cells (EPCs) may instead contribute to endogenous vascular repair. Thymosin beta-4 (TB4), a G-actin-sequestering peptide, may enhance EPC function. We hypothesize that TB4 treatment can improve the number and function of EPCs isolated from diabetic and obese patients.
Methods: Peripheral blood mononuclear cells were isolated from non-diabetic and lean (Group A: HbA1c: 5.8 ± 0.3%; BMI: 20.2 ± 2.5kg/m2; n=17), diabetic and lean (Group B: HbA1c: 6.5 ± 0.7%; BMI: 21.8 ± 2.8kg/m2; n=13), non-diabetic and obese (Group C: HbA1c: 5.3 ± 0.8%; BMI: 31.8 ± 2.7kg/m2; n=13) and diabetic and obese (Group D: HbA1c: 8.1 ± 2.2%; BMI: 29.0 ± 4.4kg/m2; n=14) patients using Ficoll density gradient centrifugation and grown on fibronectin-coated plates. Enumeration of EPCs was performed using flow cytometry of CD34+ and KDR+ markers. Colony forming unit (CFU) assay was conducted to determine EPC function. EPCs were treated with TB4 (1000ng/mL) for 3 days.
Results: At baseline, there is significantly higher CD34+/KDR+ EPCs and CFU in patients from Group C compared to Group B and D patients but lower compared Group A subjects (Table, all Ps<0.05). With TB4 treatment, there was consistent improvement in CD34+/KDR+ EPCs and CFU in all groups but most significantly in Group C. These increases restore EPC number and function to baseline level of Group A subjects (Table, all Ps<0.05).
Conclusion: The presence of diabetes mellitus whether in lean or obesity results in worst effects on EPC number and function. Improvement with TB4 treatment occurs in all 4 groups, suggesting potential therapeutic role of TB4 in reducing endothelial dysfunction in diabetes and obesity.
- © 2013 by American Heart Association, Inc.