Signal Transduction Mechanisms in Vascular Smooth Muscle Cells

Vascular smooth muscle cells (VSMCs) line the walls of blood vessels and govern vascular tone, blood pressure and vessel remodelling through complex signal transduction pathways. Extracellular stimuli such as vasoactive hormones, growth factors and mechanical stress activate G protein-coupled receptors and receptor tyrosine kinases on the VSMC surface. Downstream effectors include phospholipase C, which generates inositol trisphosphate and diacylglycerol to mobilise intracellular calcium and activate protein kinase C, and the mitogen-activated protein kinase (MAPK) cascade, which regulates gene expression, cell proliferation and migration. Reactive oxygen species (ROS) formed by NADPH oxidases modulate receptor transactivation and redox-sensitive kinases. Parallel pathways involve cyclic nucleotides—cGMP and cAMP—elicited by nitric oxide and natriuretic peptides, which oppose constrictive and proliferative signals via protein kinases G and A respectively. Crosstalk between these cascades orchestrates phenotypic switching of VSMCs from a contractile to a synthetic state, a process fundamental to hypertension, atherosclerosis and restenosis. Recent advances have revealed nuanced roles for ROS-mediated receptor activation, G protein subunit regulation and epigenetic modifiers in fine-tuning VSMC responses, offering new therapeutic avenues for cardiovascular disease.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Signal Transduction Mechanisms in Vascular Smooth Muscle Cells publication trend

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

Technical terms

Vascular smooth muscle cell (VSMC): Contractile cell type in blood vessel walls that regulates vessel diameter and blood flow.

Reactive oxygen species (ROS): Chemically reactive molecules derived from oxygen that modulate signal transduction and can induce oxidative stress.

Mitogen-activated protein kinase (MAPK): A signalling cascade controlling gene expression, cell growth and differentiation in response to extracellular stimuli.

Natriuretic peptide receptor-C (NPR-C): A non-guanylyl cyclase receptor for natriuretic peptides that influences cAMP levels and G protein signalling.

Protein kinase C (PKC): A family of serine/threonine kinases activated by diacylglycerol and calcium, involved in numerous cellular processes including proliferation.

References

1. Natriuretic Peptide Receptor-C Agonist Attenuates the Expression of Cell Cycle Proteins and Proliferation of Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rats: Role of Gi Proteins and MAPkinase/PI3kinase Signaling. PLOS ONE (2013).
2. Contribution of oxidative stress and growth factor receptor transactivation in natriuretic peptide receptor C-mediated attenuation of hyperproliferation of vascular smooth muscle cells from SHR. PLOS ONE (2018).
3. Natriuretic peptide receptor‐C‐mediated attenuation of vascular smooth muscle cell hypertrophy involves Gqα/PLCβ1 proteins and ROS‐associated signaling. Pharmacology Research & Perspectives (2017).
4. Inhibition of overexpression of Giα proteins and nitroxidative stress contribute to sodium nitroprusside‐induced attenuation of high blood pressure in SHR. Physiological Reports (2018).
5. Ligand-independent trans-Activation of the Platelet-derived Growth Factor Receptor by Reactive Oxygen Species Requires Protein Kinase C-δ and c-Src*. Journal of Biological Chemistry (2002).