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Diabetes and obesity are associated with endothelial dysfunction. As mature endothelial cells have limited regenerative capacity, endothelial progenitor cells (EPCs) may contribute to endogenous vascular repair and thymosin beta–4 (TB–4) may enhance EPC function. We aim to determine the number and function of EPCs in Zucker Diabetic Fatty (ZDF) rats and examine the effect of TB–4, comparing to Zucker Lean (ZL) controls.
8–10mL of blood was collected from 20 ZDF and 21 ZL rats. Mononuclear cells were isolated 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, migration and tubule formation assays were conducted to determine EPC function. Cells were treated with TB–4 (10ng/mL) at day 7 for all experiments for 3 days.
At baseline (pre–TB–4), there was significant increase in body weight (641±37g vs 434±36g, p<0.0001) and blood glucose levels (21.2±3.2mmol/L vs 9.4±1.4mmol/L, p<0.0001) in ZDF rats compared to their lean controls. Both EPC number and function were significantly reduced for ZDF rats compared to ZL rats (p <0.05). TB–4 treatment significantly enhanced EPC migration in both ZDF and ZL animals and increased tubule length for ZDF rats.
EPC number and function of in ZDF model were significantly reduced and TB–4 may be a potential novel target in improving EPC migration and tubule formation in diabetes and obesity.
Effect of Thymosin Beta–4 Treatment on EPC Number and Function in ZDF and ZL Rats
|Zucker Diabetic Fatty (ZDF)||Zucker Diabetic Fatty (ZDF)||Zucker Lean (ZL)||Zucker Lean (ZL)|
|Average colony forming unit||1.5 ± 0.5||2.0 ± 0.1||0.45||2.2 ± 0.8||2.5 ± 0.5||0.13|
|Migrated cell||6.0 ± 1.7||7.3 ± 1.5||0.002||9.2 ± 2.3||10.8 ± 2.4||0.015|
|Mean tubule length per mm2||3.6 ± 0.5||4.8 ± 0.5||0.03||4.8 ± 0.9||5.2 ± 0.6||0.27|
Poster Sessions, Expo North
Sunday, March 10, 2013, 3:45 p.m.–4:30 p.m.
Session Title: Angiogenesis and Vascular Injury
Abstract Category: 33. Vascular Medicine: Basic
Presentation Number: 1254–169
- 2013 American College of Cardiology Foundation