Abstract
Endothelial progenitor cells (EPCs) are bone-marrow derived cells that are critical in the maintenance of endothelial wall integrity and protection of ischemic myocardium through the formation of new blood vessels (vasculogenesis) or proliferation of pre-existing vasculature (angiogenesis). Diabetes mellitus (DM) and the metabolic syndrome are commonly associated with ischemic heart disease through its pathological effects on the endothelium and consequent endothelial dysfunction. Thymosin-β4 (Tβ4) which expressed in the embryonic heart is critical in epicardial and coronary artery formation. In this study, we explored the effects of Tβ4 treatment on diabetic EPCs in vitro and intramyocardial injection of Tβ4-treated and non-Tβ4 treated EPCs following acute myocardial infarction (MI) of diabetic rats in vivo. It was found that 10 ng/mL Tβ4 increased migration, tubule formation, and angiogenic factor secretion of diabetic EPCs in vitro. In vivo, although implantation of Tβ4 treated diabetic EPCs significantly increased capillary density and attracted more c-Kit positive progenitor cells into the infarcted hearts as compared with implantation of non-Tβ4 treated diabetic EPCs, the significantly improved left ventricular ejection fraction was only found in the rats which received non-Tβ4 treated EPCs. The data suggests that a low dose Tβ4 increases diabetic EPC migration, tubule formation, and angiogenic factor secretion. However, it did not improve the effects of EPCs on left ventricular pump function in diabetic rats with MI.
Highlights
Diabetes mellitus is a common metabolic disease with a high and growing prevalence affecting 4%of the population [1]
It was found that 10 ng/mL Tβ4 significantly enhanced tubular formation capability of Endothelial progenitor cells (EPCs)
It has been shown that Tβ4 plays important roles in promoting cell migration, proliferation and neovascularization and paracrine signals for endogenous stem cell recruitment to assist in wound repair [18]
Summary
Diabetes mellitus is a common metabolic disease with a high and growing prevalence affecting 4%. Of the population [1]. Around 171 million people were affected in 2000 and 366 million are expected in 2030 worldwide [1]. Diabetes mellitus (DM) causes endothelial dysfunction and is associated with an increased risk of cardiovascular disease [2]. Endothelial dysfunction comprises several malfunctions in the vascular endothelium and plays a primary role in the development of vascular complications associated with diabetes and cardiovascular disease [3]. Hyperglycemia, dyslipidemia, hyperinsulinemia, and inflammation are characteristic features of both types 1 and 2 diabetes.
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