%0 Journal Article
%T Regulation of EPCs: The Gateway to Blood Vessel Formation
%A Kate A. Parham
%A Stuart M. Pitson
%A Claudine S. Bonder
%J New Journal of Science
%D 2014
%R 10.1155/2014/972043
%X Endothelial progenitor cells (EPCs) are primitive endothelial precursors which are known to functionally contribute to the pathogenesis of disease. To date a number of distinct subtypes of these cells have been described, with differing maturation status, cellular phenotype, and function. Although there is much debate on which subtype constitutes the true EPC population, all subtypes have endothelial characteristics and contribute to neovascularisation. Vasculogenesis, the process by which EPCs contribute to blood vessel formation, can be dysregulated in disease with overabundant vasculogenesis in the context of solid tumours, leading to tumour growth and metastasis, and conversely insufficient vasculogenesis can be present in an ischemic environment. Importantly, it is widely known that transcription factors tightly regulate cellular phenotype and function by controlling the expression of particular target genes and in turn regulating specific signalling pathways. This suggests that transcriptional regulators may be potential therapeutic targets to control EPC function. Herein, we discuss the observed EPC subtypes described in the literature and review recent studies describing the role of a number of transcriptional families in the regulation of EPC phenotype and function in normal and pathological conditions. 1. Introduction The endothelial cell (EC) lined blood vasculature plays a vital role in maintaining vascular integrity, mediating pro- and anticoagulation and controlling immune cell trafficking (reviewed in [1, 2]). Precursors of ECs, namely, endothelial progenitor cells (EPCs), are integral contributors to vascular repair and neovascularisation [3], maintaining vascular homeostasis. Vasculogenesis is the process by which EPCs contribute to de novo blood vessel formation and is originally thought to only occur prenatally. However, in 1997, Asahara and colleagues identified EPCs in the adult, thereby revealing a role of these cells in postnatal vasculogenesis [4, 5]. Briefly, during vasculogenesis, bone marrow (BM) resident EPCs are mobilised into the circulation [5, 6] in response to EPC-activation factors which are upregulated in the circulating blood in response to hypoxia and vessel damage [7, 8]. Once in the circulation, EPCs traffic to sites in need of blood vessel formation and/or repair where they contribute to vasculogenesis (reviewed in [2]) by (1) an autocrine process of differentiating into a mature EC and incorporating into the vasculature [9, 10] or (2) a paracrine process by secreting proangiogenic factors [11, 12]. Although EPCs
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