Abstract 13054: Thymosin Beta-4-Treated Endothelial Progenitor Cells Improve Cardiac Function and Vasculogenesis in Diabetic Obese Rats with Myocardial Infarction
Introduction: Diabetes and obesity are associated with endothelial dysfunction and may impair circulating endothelial progenitor cells (EPCs). Thymosin beta-4 (Tβ4), a novel peptide with angiogenic properties, may improve EPC number and function.
Hypothesis: We aim to transplant allogenic Tβ4-treated EPCs in Zucker Diabetic Fatty (ZDF) rats with myocardial infarction (MI) and hypothesize that Tβ4-treated EPCs may improve cardiac function, vasculogenesis and upregulate angiogenic cytokines and genes, compared to non-treated EPCs and controls.
Methods: The left anterior descending coronary artery was permanently ligated to induce experimental MI on ZDF rats (n=19), divided into MI+saline(n=6); MI+EPCs (n=6) and MI+Tβ4-treated EPCs (n=7). Peripheral blood mononuclear cells were harvested from ZDF rats and isolated using Ficoll density gradient centrifugation and grown on fibronectin-coated plates. EPCs were treated with Tβ4 (1μg/mL) on day 7. At day 10, allogenic EPCs were harvested and transplanted into the peri-infarcted myocardium. Echocardiographic examination including strain assessment, immunohistological assessments and assays of angiogenic cytokines were performed 6 weeks after surgery.
Results: Left ventricular (LV) ejection fraction was improved in Tβ4-treated EPCs (72.0±7.6%) and non-treated EPCs rats (80.5±5.9%) compared to control MI rats (64.8±19.7%) (P=0.04). Similar improvement was observed in LV radial strain rate in rats with Tβ4-treated EPCs (-7.22±1.24 1/s) and non-treated EPCs (-6.67±2.66 1/s) compared to MI only (-4.08±3.75 1/s) (P<0.01). Vascular density (CD31) and c-kit density (CD117) were significantly upregulated in Tβ4-treated EPCs rats compared to MI (P=0.03; P=0.005 respectively) and non-treated EPCs rats (P=0.04; P=0.04 respectively). Angiogenic cytokines of PDGF-BB, IGF-1 and VEGF levels were increased by 1.5 fold in Tβ4-treated EPCs and supported by similar trend in mRNA levels compared to non-treated EPCs (P<0.01).
Conclusions: ZDF rats with Tβ4-treated EPCs had significant improvement in cardiac function, increased vasculogenesis and upregulation of angiogenic cytokines and genes. This suggests that Tβ4 may be beneficial in enhancing efficacy of EPCs in cell-based therapies.
Author Disclosures: P.S. Lee: None. L. Ye: None. Y. Chen: None. E. Khoo: None. T. Yeo: None. H. Tan: None. A. Richards: None. K. Poh: None.
- © 2014 by American Heart Association, Inc.