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Review
. 2024 Oct 23:12:1446452.
doi: 10.3389/fcell.2024.1446452. eCollection 2024.

Mechanosensory entities and functionality of endothelial cells

Claudia Tanja Mierke  1
Affiliations
Review

Mechanosensory entities and functionality of endothelial cells

Claudia Tanja Mierke. Front Cell Dev Biol. .

Abstract

The endothelial cells of the blood circulation are exposed to hemodynamic forces, such as cyclic strain, hydrostatic forces, and shear stress caused by the blood fluid's frictional force. Endothelial cells perceive mechanical forces via mechanosensors and thus elicit physiological reactions such as alterations in vessel width. The mechanosensors considered comprise ion channels, structures linked to the plasma membrane, cytoskeletal spectrin scaffold, mechanoreceptors, and junctional proteins. This review focuses on endothelial mechanosensors and how they alter the vascular functions of endothelial cells. The current state of knowledge on the dysregulation of endothelial mechanosensitivity in disease is briefly presented. The interplay in mechanical perception between endothelial cells and vascular smooth muscle cells is briefly outlined. Finally, future research avenues are highlighted, which are necessary to overcome existing limitations.

Keywords: endothelial cell anisotropy; fluid shear stress; forces; integrins; ion channels; mechanoreceptors; stiffness; vascular function.

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Conflict of interest statement

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

FIGURE 1
FIGURE 1
Various endothelial cell functions in the vascular system.
FIGURE 2
FIGURE 2
Endothelial nitric oxide synthetase (eNOS)-generated nitric oxide (NO) provides atheroprotective characteristics.
FIGURE 3
FIGURE 3
Types of endothelial mechanoreceptors at their luminal site are permanently subject to vascular mechanical forces. The sensing of these forces can be performed through specific mechanosensors. Among them are ion channels, such as Piezo1, transient receptor potential vanilloid 4 channel (TRPV4), K+ channel inwardly rectifying 2.1 (Kir 2.1), epithelial sodium channel (ENaC), TREK-1, DDR1, CD44, and mechanoreceptors, comprising the G-protein-coupled receptor (GPCR).
FIGURE 4
FIGURE 4
The apical surface of the endothelial cell possesses mechanosensory proteins, such as Plexin D1, NOTCH, Piezo1, P2X4, DDR1, CD44, and G protein-coupled receptors, such as GPR68 and mechanosensitive structures like caveolar, glycocalyx, and primary cilia. Cell–cell junctions, such as adherens junctions, compromise VE-cadherin, PECAM-1, vascular endothelial growth factor 2 (VEGFR2), and VEGFR3. At the basal site of the endothelium is the contact to the basement membrane via integrins, such as α5β1 , which also act as mechanosensors. All these mechanosensors contribute to mechanotransduction processes, including the PI3K-Akt pathway, YAP-TAZ pathway, ERK1-ERK2 pathway, and Rho signal transduction pathway. Several mechanotransduction routes lead to the activation of transcription factors, such as Krüppel-like factor (KLF2) and KLF4, hypoxia-inducible factor 1 α , and nuclear factor- κ B (NF- κ B); endothelial-to-mesenchymal transition (EndMT); junctional adhesion molecule (JAM); focal adhesion kinase (FAK); endothelial nitric oxide synthetase (eNOS); reactive oxygen species (ROS); transcription factor SOX13; and nuclear factor erythroid 2-related factor 2 (NRF2). The mechanosensors affect multiple endothelial vascular functions and can lead to diseases upon the perturbed flow, such as cancer and atherosclerosis.
FIGURE 5
FIGURE 5
Vascular interference is regulated by shear flow. Shear stress can alter the endothelial cell function via endothelial mechanosensing and mechanotransduction events to govern the epigenome, transcriptome, phenotype, and interplay between endothelial cells and VSMCs and other adjacent cells, such as macrophages. The regulation of this interferences results in homeostasis under normal conditions, and in pathological conditions, it leads to diseases. lncRNAs, long non-coding RNAs.
FIGURE 6
FIGURE 6
The net filtration takes place close to the arterial end of the capillary, when capillary hydrostatic pressure (CHP) is larger than the blood colloidal osmotic pressure (BCOP). There is no motion of fluid near the midpoint (CHP = BCOP). Net reabsorption takes place close to the venous end of the capillary (BCOP is larger than CHP).
FIGURE 7
FIGURE 7
Development of diseases such as atherosclerosis: the behavior of endothelial cells is guided by dynamics of the vascular microenvironment. Most commonly, vessel walls are subject to uniform/laminar/stable flow that fosters the healthy state of endothelial cells. Vessel bifurcations and curvatures can lead to perturbed flow areas, which cause altered endothelial cells with development toward a diseased behavior. For instance, endothelial cells possess hyperpermeability, and they get proinflammatory. Consequently, endothelial cells enable the transmigration of low-density lipoprotein (LDL) and immune cells into the blood vessel wall, whereby atherosclerotic plaques can be built-up.
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References

    1. AbouAlaiwi W. A., Takahashi M., Mell B. R., Jones T. J., Ratnam S., Kolb R. J., et al. (2009). Ciliary polycystin-2 is a mechanosensitive calcium channel involved in nitric oxide signaling cascades. Circulation Res. 104, 860–869. 10.1161/CIRCRESAHA.108.192765 - DOI - PMC - PubMed
    1. Adil M. S., Narayanan S. P., Somanath P. R. (2021). Cell-cell junctions: structure and regulation in physiology and pathology. Tissue Barriers 9, 1848212. 10.1080/21688370.2020.1848212 - DOI - PMC - PubMed
    1. Aghajanian H., Choi C., Ho V. C., Gupta M., Singh M. K., Epstein J. A. (2014). Semaphorin 3d and Semaphorin 3e Direct Endothelial Motility through Distinct Molecular Signaling Pathways. J. Biol. Chem. 289, 17971–17979. 10.1074/jbc.M113.544833 - DOI - PMC - PubMed
    1. Agre P., Orringer E. P., Bennett V. (1982). Deficient red-cell spectrin in severe, recessively inherited spherocytosis. N. Engl. J. Med. 306, 1155–1161. 10.1056/NEJM198205133061906 - DOI - PubMed
    1. Ahmad T., Ertuglu L. A., Masenga S. K., Kleyman T. R., Kirabo A. (2023). The epithelial sodium channel in inflammation and blood pressure modulation. Front. Cardiovasc. Med. 10, 1130148. 10.3389/fcvm.2023.1130148 - DOI - PMC - PubMed

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