Signaling Pathways in Vascular Smooth Muscle Cells

Vascular smooth muscle cells (VSMCs) line the medial layer of blood vessels and govern vascular tone, blood pressure and structural remodelling. Their capacity to contract, proliferate and secrete extracellular matrix is orchestrated by a network of signalling pathways triggered by mechanical forces, circulating hormones and inflammatory mediators. Classical G protein-coupled receptors (GPCRs) activate heterotrimeric G proteins that drive phospholipase C, cyclic AMP and Rho kinase cascades, while receptor tyrosine kinases (RTKs) engage mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase/Akt axes. Transforming growth factor-β (TGF-β) family receptors elicit Smad transcription factor phosphorylation, linking extracellular cues to nuclear gene programmes controlling matrix synthesis and differentiation state. Growing evidence reveals extensive cross-talk between GPCRs and kinase receptors via transactivation, in which proteases or matrix metalloproteinases liberate growth factor ligands or directly modify adjacent receptors. β-Arrestin scaffolds further diversify signalling outcomes by recruiting kinases and ubiquitin ligases independent of G protein activity. Such interwoven pathways guide VSMC phenotypic switching from a contractile to a synthetic state, underpinning adaptive remodelling in health and maladaptive processes in hypertension, atherosclerosis and restenosis. Understanding these signalling modules holds promise for targeted interventions to restore vascular homeostasis and mitigate global cardiovascular disease burden.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Signaling Pathways in Vascular Smooth Muscle Cells publication trend

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

Technical terms

G protein-coupled receptor (GPCR): A cell-surface receptor that activates intracellular G proteins upon ligand binding, initiating multiple second-messenger cascades.

Transactivation: Indirect activation of one receptor type by another, often via proteolytic release of ligands or receptor modification, leading to cross-coupling of signalling pathways.

Smad transcription factors: Intracellular effectors phosphorylated by TGF-β family receptors, which translocate to the nucleus to regulate gene expression.

Proteoglycan: A macromolecule comprising a core protein and covalently attached glycosaminoglycan chains, essential for extracellular matrix structure and lipid binding.

Gαq subunit: A G protein α-subunit that couples specific GPCRs to phospholipase C and can also mediate receptor transactivation, influencing VSMC phenotype.

References

1. Lipopolysaccharide acting via toll-like receptor 4 transactivates the TGF-β receptor in vascular smooth muscle cells. Cellular and Molecular Life Sciences (2022).
2. Gαq Is the Specific Mediator of PAR-1 Transactivation of Kinase Receptors in Vascular Smooth Muscle Cells. International Journal of Molecular Sciences (2022).
3. Smad transcription factors as mediators of 7 transmembrane G protein-coupled receptor signalling. Acta Pharmacologica Sinica (2024).