Part of the book: Gestational Diabetes
Human endothelial progenitor cells (hEPCs) are adult stem cells, located in the bone marrow and peripheral blood. These cells can be differentiated into mature endothelial cells, which are involved in processes of angiogenesis and vessel regeneration. Different phenotypes and subtypes of endothelial progenitor cells (EPCs), such as early and late EPCs, have been described according to their functionality. Thus, it has been shown that early EPCs release cytokines that promote tissue regeneration and neovasculogenesis, whereas late EPC and endothelial colony forming cells (ECFCs) contribute to the formation of blood vessels and stimulate tube formation. It has been demonstrated that the number of circulating hEPC is decreased in individuals with hypercholesterolemia, hypertension, and/or diabetes. In addition, the number and the migratory activity of these cells are inversely correlated with risk factors such as hypertension, hypercholesterolemia, diabetes, and metabolic syndrome. On the other hand, the number of circulating hEPC is increased in hypoxia or acute myocardial infarction (AMI). hEPCs have been used for cell-based therapies due to their capacity to contribute in the re-endothelialization of injured blood vessels and neovascularization in ischemic tissues. This chapter provides an overview of the key role of hEPC in promoting angiogenesis and their potential use for cell therapy.
Part of the book: Microcirculation Revisited
Fluid shear stress (FSS) is able to generate phenotypic changes in the cells in direct contact with the strain force. In order to detect and transduce FSS into intracellular pathways, biological systems use a specific set of sensors, called mechanosensors. The process involves the conversion of the mechanical force into a chemical or electrical signal. Primary cilium is a non-motile organelle that emanates from the cell surface of most mammalian cell types that act as a mechanosensor. Increasing evidence suggests that primary cilia are key coordinators of signaling pathways in tissue homeostasis and when defective may cause human diseases and developmental disorders. Here, we will describe the endothelial primary cilium as a mechanotransductory organelle sensing FSS. To fulfill this function, primary cilium requires the localization of mechanoproteins, polycystin-1 and -2, in their membrane and the structural gene product, polaris. Physiologically, deflection of primary cilium increases the intracellular calcium concentration triggering a signaling pathway that leads to nitric oxide (NO) formation and vasodilation. Additionally, ciliopathies, such as polycystic kidney disease and atherosclerosis, will also be discussed. We also analyze available information regarding a trio of membrane receptors involved in FSS sensing and transducing such as vascular endothelial growth factor receptors (VEGFRs) and its coreceptor neuropilin (NRP), as well as purinergic receptors (P2Y2). Whether or not they modulate, the primary cilium role in sensing FSS is poorly understood. This chapter highlights the main relevance of primary cilium in sensing blood flow, although exact mechanisms are not fully known yet.
Part of the book: Endothelial Dysfunction
HOX genes belong to a family of transcription factors characterized by a 183 bp DNA sequence called homeobox, which code for a 61-amino-acid domain defined as the homeodomain. These genes play a central role during embryonic development by controlling body organization, organogenesis, and stem cell differentiation. They can also play a role in adult processes such as embryo implantation, hematopoiesis, and endothelial differentiation. Since endothelial cell differentiation is one of the main steps to initiate vasculogenesis and angiogenesis, we analyzed the role of several Hox genes in the regulation of these two processes. In this chapter, we summarized the evidence to support the function of Hox genes in adult tissues, specifically in endothelial cell differentiation, by studying their mechanism of action and how their target genes regulate vasculogenesis and angiogenesis. Understanding the cellular and molecular mechanisms triggered by Hox biological effects is pivotal for designing new drugs or therapies for high prevalent pathologies, such as cardiovascular diseases.
Part of the book: Endothelial Dysfunction