Journal of Clinical and Molecular Endocrinology

Keywords

Diabetes mellitus, Endothelial progenitor cells, Endothelial dysfunction, Reparation

Introduction

Diabetes Mellitus (DM) is a powerful risk factor of early atherosclerosis, Cardiovascular (CV) disease, renal disease and heart failure [1]. There is a large body of evidence regarding that the hyperglycemia, lipotoxicity and hypoxia initiate the microvascular inflammation, induce endothelial dysfunction and impair endothelium [2,3]. Normally, the endothelial repair is result in several multifunctional relations, which in particularly include mobbing, differentiation and proliferation of Endothelial Progenitor Cells (EPCs) derived from bone marrow and peripheral tissues [4,5]. EPCs may cumulatively express on their surface various specific endothelial antigens like hematopoietic stem cells (CD34, CD133, AC133) and endothelial cell markers predominantly VEGF receptor-2, while expression of “nonclassical” markers (CD45, Tei2 and Flt-1) could be found also [6]. Nevertheless, two main subsets of EPCs labeled as early EPCs and late outgrowth EPCs distinguish each other by their markers’ presentation and the role in angiogenesis and vascularization [7,8]. Low number and weak functionality (i.e., reduced ability to proliferation, differentiation, adhesion, migration, incorporation into tubular structures, and survival) of EPC known as “impaired phenotype” were found in diabetics, whereas in the patients with increased number of EPCs was determined frequently [9,10]. Recent studies have shown that in subjects with known DM a dysfunction EPCs associated with neither their low numbers, nor their weak functions is a marker of CV risk and DM-related complications [11]. However, it has been found that subset of circulating CD34(+) cells expressing VEGFR2 and CD133 was a phenotypically and functionally distinct population of circulating EPCs that may influence on the reparation and angiogenesis [12,13].

DM is characterized reduced expression of angiopoetic factors and shaped an “impaired phenotype” of EPC signature as a result in mutual molecular mechanisms affected cellular signal systems, paracrine regulations and epigenetic modification. The dysfunction of EPCs correlates well with traditional CV risk factors, DM-related angiopathy and CV events [14-16]. Moreover, EPCs dysfunction may be a useful predictive tool for evaluating the CV risk including risk of death in general population and amongst individuals with known CV and T2DM [17].

Finally, dysfunction of EPCs, which reflects worsening endothelial repair in T2DM, accompanies with CV/DM-related outcomes and may help to identify diabetics at increased CV risk. Large clinical studies are required to more pretty accurate evaluate the role of EPCs’ dysfunction as a predictive tool in diabetics.

References

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