Endothelin Signaling in Vascular Smooth Muscle Function

Endothelin signalling in vascular smooth muscle constitutes a central mechanism by which the endothelium regulates vascular tone, structure and remodelling. The 21-amino-acid peptide endothelin-1 (ET-1) is released by endothelial cells and acts primarily through two G protein-coupled receptors, ETA and ETB, expressed on vascular smooth muscle cells (VSMCs). Receptor activation triggers phospholipase C-mediated inositol trisphosphate production, intracellular calcium mobilisation and activation of protein kinase C alongside mitogen-activated protein kinase (MAPK) cascades. These pathways converge to elicit potent and sustained vasoconstriction, to drive VSMC proliferation and migration, and to promote phenotypic switching from a contractile to a synthetic state. In health, endothelin signalling contributes to basal vascular tone and autoregulatory adjustments. In disease, exaggerated ET-1 production and receptor expression underpin hypertension, atherosclerosis, post-angioplasty restenosis and pulmonary arterial hypertension. Chronic receptor activation fosters neointimal formation, adverse extracellular matrix remodelling and inflammatory cell recruitment. Pharmacological antagonism of ETA and ETB receptors has thus emerged as a therapeutic strategy to lower blood pressure, to stabilise atherosclerotic plaques and to mitigate vascular remodelling. Current efforts aim to refine receptor-selective antagonists, to develop molecular imaging probes for receptor expression and to elucidate cross-talk between endothelin and other vasoactive systems for integrated cardiovascular protection.

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Endothelin Signaling in Vascular Smooth Muscle Function publication trend

The graph below shows the total number of articles in endothelin signaling in vascular smooth muscle function across all publications each year (not limited to Nature Index journals).

Technical terms

Endothelin-1 (ET-1): A 21-amino-acid peptide produced by endothelial cells that potently induces vasoconstriction.

ETA receptor: A G protein-coupled receptor on vascular smooth muscle cells mediating sustained vasoconstriction and proliferation.

ETB receptor: A G protein-coupled receptor that can mediate vasoconstriction on smooth muscle and clearance of ET-1 via the endothelium.

Vascular smooth muscle cell (VSMC): A specialised cell in the vessel wall responsible for contractility, vessel tone and structural remodelling.

Mitogen-activated protein kinase (MAPK): A signalling cascade (including ERK1/2, p38, JNK) that regulates cell proliferation, differentiation and stress responses.

Atherosclerosis: A chronic inflammatory disease characterised by lipid-rich plaque formation, vascular remodelling and potential plaque rupture.

References

1. The Anti-Atherosclerotic Effects of Endothelin Receptor Antagonist, Bosentan, in Combination with Atorvastatin—An Experimental Study. International Journal of Molecular Sciences (2024).
2. Monitoring Endothelin-A Receptor Expression during the Progression of Atherosclerosis. Biomedicines (2020).
3. Enhanced Endothelin A and B Receptor Expression and Receptor‐Mediated Vasoconstriction in Rat Mesenteric arteries after Lipopolysaccharide Challenge. Mediators of Inflammation (2019).