Abstract
As a cellular interface between the blood and tissues, the endothelial cell (EC) monolayer is involved in the control of key functions including vascular tone, permeability and homeostasis, leucocyte trafficking and hemostasis. EC regulatory functions require long-distance communications between ECs, circulating hematopoietic cells and other vascular cells for efficient adjusting thrombosis, angiogenesis, inflammation, infection and immunity. This intercellular crosstalk operates through the extracellular space and is orchestrated in part by the secretory pathway and the exocytosis of Weibel Palade Bodies (WPBs), secretory granules and extracellular vesicles (EVs). WPBs and secretory granules allow both immediate release and regulated exocytosis of messengers such as cytokines, chemokines, extracellular membrane proteins, coagulation or growth factors. The ectodomain shedding of transmembrane protein further provide the release of both receptor and ligands with key regulatory activities on target cells. Thin tubular membranous channels termed tunneling nanotubes (TNTs) may also connect EC with distant cells. EVs, in particular exosomes, and TNTs may contain and transfer different biomolecules (e.g., signaling mediators, proteins, lipids, and microRNAs) or pathogens and have emerged as a major triggers of horizontal intercellular transfer of information.
Highlights
Luisa BalestrieriLining all blood vessels of the vascular tree, the endothelium represents a surface area of around 5000 m2 composed of roughly 1014 endothelial cells (ECs) and can be perceived as an organ system [1]
ECs stimulated with transforming growth factor (TGF)-β induced the shedding of VEGFR2-containing exosomes, which regulate the effects of angiogenic stimuli on vascular sprouting [89]
ECs possess a multilevel machinery to deliver messages to distant cells such as cells circulating in the blood vessel including platelets, leucocytes, other vascular cells, or normal and tumor cells in tissues
Summary
Lining all blood vessels of the vascular tree, the endothelium represents a surface area of around 5000 m2 composed of roughly 1014 endothelial cells (ECs) and can be perceived as an organ system [1]. At the interface between the blood and tissues, the EC layer is involved in the control of key functions including vascular tone, permeability and homeostasis, leucocyte trafficking and hemostasis [2,3] To ensure this broad variety of functions in different vascular beds and tissues, ECs display marked heterogeneity in both structure and function [4,5,6,7,8,9]. EC respond to a large variety of stimuli by adapting both their phenotype and their functions to preserve vascular integrity [13,14,15] To this aim, EC display at the cell surface specific receptors that will sense extracellular signals to initiate specific changes in EC phenotype and functions. The aim of this review is to provide an overview of some of the advances in our molecular and functional understanding of the secretory pathways, granules and extracellular vesicles, generating the endothelial secretome, and of TNTs used for intercellular communication between ECs and distant cells
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