Abstract
The endothelial surface is a highly flexible signaling hub which is able to sense the hemodynamic forces of the streaming blood. The subsequent mechanosignaling is basically mediated by specific structures, like the endothelial glycocalyx building the top surface layer of endothelial cells as well as mechanosensitive ion channels within the endothelial plasma membrane. The mechanical properties of the endothelial cell surface are characterized by the dynamics of cytoskeletal proteins and play a key role in the process of signal transmission from the outside (lumen of the blood vessel) to the interior of the cell. Thus, the cell mechanics directly interact with the function of mechanosensitive structures and ion channels. To precisely maintain the vascular tone, a coordinated functional interdependency between endothelial cells and vascular smooth muscle cells is necessary. This is given by the fact that mechanosensitive ion channels are expressed in both cell types and that signals are transmitted via autocrine/paracrine mechanisms from layer to layer. Thus, the outer layer of the endothelial cells can be seen as important functional mechanosensitive and reactive cellular compartment. This review aims to describe the known mechanosensitive structures of the vessel building a bridge between the important role of physiological mechanosignaling and the proper vascular function. Since mutations and dysfunction of mechanosensitive proteins are linked to vascular pathologies such as hypertension, they play a potent role in the field of channelopathies and mechanomedicine.
Highlights
Maintaining vascular homeostasis and keeping blood pressure variations in an optimal physiological range are a lifelong challenge which among others ensure a sufficient blood flow and supply of oxygen and nutrients to peripheral organs
This review mainly focuses on the impact of the endothelial glycocalyx and mechanosensitive ion channels in endothelial mechanosensing
Proper regulation of the vessel tone is the basis of cardiovascular health
Summary
Maintaining vascular homeostasis and keeping blood pressure variations in an optimal physiological range are a lifelong challenge which among others ensure a sufficient blood flow and supply of oxygen and nutrients to peripheral organs. Endothelial cells (EC) are located at the innermost layer of all blood and lymphatic vessels They are constantly exposed to mechanical forces mediated by the blood flow, thereby maintaining a selective permeable barrier between the tissue and intravascular lumen. Even at the level of EC, there is a distinct spatial distribution of the external forces acting on different cellular mechanosensors. These mechanical forces are sensed and translated into biochemical signals by specific structures and proteins located in the membranes of endothelial cells. A number of potential cellular mechanosensitive and responsive structures have been identified so far, Pflugers Arch - Eur J Physiol (2020) 472:419–433 including cell adhesion proteins (like VE-Cadherin, PECAM1), ion channels, tyrosine kinase receptors (VEGF receptor 2), G-protein coupled receptors (GPCR), caveolae, primary cilia, cytoskeletal actin, nesprins, integrins, and the endothelial glycocalyx (eGC) [43, 81, 193]
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