Endothelial Cell Mechanotransduction Under Shear Stress

The vascular endothelium is exquisitely sensitive to the mechanical forces generated by blood flow. Shear stress, the tangential frictional force imposed on endothelial surfaces, is transduced into biochemical signals via specialised structures such as the glycocalyx, caveolae and junctional complexes. Mechanotransduction involves activation of ion channels, integrins and G-protein-coupled receptors, leading to mobilisation of intracellular calcium, generation of reactive oxygen species and recruitment of cytoskeletal adaptors. Downstream signalling cascades include phosphoinositide 3-kinase–Akt, mitogen-activated protein kinases (MAPKs) and Rho family GTPases. These pathways converge on transcriptional regulators such as Krüppel-like factors and nuclear factor κB to modulate gene programmes governing nitric oxide synthesis, cell alignment, barrier integrity and inflammatory responses. Laminar shear promotes an atheroprotective phenotype characterised by sustained endothelial nitric oxide synthase (eNOS) activation and anti-inflammatory gene expression, whereas disturbed or oscillatory flow at bifurcations predisposes to endothelial dysfunction, leukocyte adhesion and atherogenesis. Understanding these processes underpins novel strategies in vascular tissue engineering, targeted therapeutics for atherosclerosis and optimisation of haemodynamic conditions in cardiovascular implants.

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Endothelial Cell Mechanotransduction Under Shear Stress publication trend

The graph below shows the total number of articles in endothelial cell mechanotransduction under shear stress across all publications each year (not limited to Nature Index journals).

Technical terms

Shear stress: frictional force exerted parallel to the endothelial surface by flowing blood.

Mechanotransduction: conversion of mechanical stimuli into intracellular biochemical signals.

Endothelial nitric oxide synthase (eNOS): enzyme that produces nitric oxide in response to shear stress, critical for vasodilation and vascular homeostasis.

Mitogen-activated protein kinases (MAPKs): a family of serine/threonine kinases that transduce mechanical and chemical signals to regulate gene expression.

Connexin 43 (Cx43): gap-junction protein whose expression is modulated by shear stress and contributes to intercellular communication and inflammation.

References

1. The Involvement of Cx43 in JNK1/2-Mediated Endothelial Mechanotransduction and Human Plaque Progression. International Journal of Molecular Sciences (2023).
2. Identification of Flow-dependent Endothelial Nitric-oxide Synthase Phosphorylation Sites by Mass Spectrometry and Regulation of Phosphorylation and Nitric Oxide Production by the Phosphatidylinositol 3-Kinase Inhibitor LY294002*. Journal of Biological Chemistry (1999).
3. Fluid Shear Stress Stimulates Big Mitogen-activated Protein Kinase 1 (BMK1) Activity in Endothelial Cells DEPENDENCE ON TYROSINE KINASES AND INTRACELLULAR CALCIUM*. Journal of Biological Chemistry (1999).