Abstract 14346: Short Term Hyperglycaemia Impair Endothelial Progenitor Cells With Improvement After Thymosin Beta-4 Treatment
Background: Hyperglycaemia, associated with endothelial dysfunction, is the leading cause of vascular complications in diabetes. Transient hyperglycaemia may occur in stress-related conditions, such as myocardial infarction or gestation. We hypothesize that endothelial progenitor cells (EPCs) may be affected by transient hyperglycaemia and that thymosin beta-4 (TB4), a G-actin-sequestering peptide, may enhance EPC number and function.
Methods: Peripheral blood mononuclear cells were isolated from healthy (n=20) subjects using Ficoll density gradient centrifugation and grown on fibronectin-coated plates. Enumeration of EPC was performed using flow cytometry of CD34+ and KDR+ markers. Migration and tubule formation assays were conducted to determine EPC function. EPCs were incubated with medium with no glucose, medium with 5.5mM glucose (normal glycaemic) or 15mM glucose (hyperglycaemic) for 5 days followed by TB4 treatment (1000ng/mL) for 3 days.
Results: At baseline, there is significantly lower percentage of CD34+ and KDR+ in EPC treated with 15mM glucose (0.25±0.03%) compared to controls (0.45 ± 0.05%; P<0.05). Furthermore, there were impairment in migration and tubule formation in the EPCs incubated under hyperglycaemic condition (Table). With TB4 treatment, there was significant improvement in all parameters in these EPCs (all Ps<0.05).
Conclusion: The number and functionality of EPCs are significantly impaired with presence of 5 days of high glucose. With TB4 treatment, the parameters improved, suggesting potential beneficial effects of TB4 in diabetes.
- © 2013 by American Heart Association, Inc.