Smooth Muscle Cell Dynamics in Cardiovascular Health

Vascular smooth muscle cells (SMCs) are fundamental organisers of vessel wall structure and function. In their contractile state, they regulate vascular tone and blood pressure through coordinated contraction and relaxation. Under pathological stimuli such as hypertension, lipid accumulation or inflammatory mediators, SMCs undergo phenotypic switching to a synthetic state, characterised by increased proliferation, migration and extracellular matrix synthesis. This plasticity enables repair of injury but also drives maladaptive remodelling, notably neointimal hyperplasia and plaque progression in atherosclerosis. Cross-talk with endothelial cells and infiltrating immune populations further amplifies inflammatory signalling and oxidative stress within the vessel wall. Mechanotransduction and epigenetic modifications modulate SMC behaviour, and emerging evidence highlights distinct subpopulations with macrophage-like or osteogenic features that contribute to chronic inflammation and vascular calcification. Understanding the balance between adaptive and maladaptive SMC responses underpins the development of targeted therapies to preserve vessel integrity and prevent cardiovascular events on a global scale.

Research from Nature Portfolio

Recent studies have demonstrated that angiotensin-(1–7) counteracts angiotensin II-driven SMC proliferation, migration and inflammatory activation by engaging the Mas receptor. This interaction suppresses reactive oxygen species-dependent PI3K/Akt and MAPK/ERK signalling, thereby attenuating neointimal growth. These findings reveal a protective axis within the renin–angiotensin system that may be harnessed to limit pathological vascular remodelling.

Smooth Muscle Cell Dynamics in Cardiovascular Health publication trend

The graph below shows the total number of articles in smooth muscle cell dynamics in cardiovascular health across all publications each year (not limited to Nature Index journals).

Technical terms

Vascular smooth muscle cell (SMC): A specialised muscle cell in the vessel media that regulates vascular tone and can switch phenotype under stress.

Phenotypic switching: The process by which SMCs transition from a contractile to a synthetic state, altering their function and gene expression.

Neointimal hyperplasia: The thickening of the vessel intima due to SMC proliferation and migration, a key feature of restenosis and atherosclerosis.

Reactive oxygen species (ROS): Chemically reactive molecules derived from oxygen that can serve as signalling mediators or cause oxidative damage.

Phenotypic plasticity: The capacity of SMCs to adopt diverse functional states, including macrophage-like or osteogenic phenotypes.

Inflammasome: A multiprotein complex that activates inflammatory caspases and cytokines in response to cellular stress.

References

1. Artesunate Inhibits Neointimal Hyperplasia by Promoting IRF4 Associated Macrophage Polarization. Advanced Science (2025).
2. Angiotensin-(1–7) abrogates angiotensin II-induced proliferation, migration and inflammation in VSMCs through inactivation of ROS-mediated PI3K/Akt and MAPK/ERK signaling pathways. Scientific Reports (2016).
3. NLRP3 inflammasome activation contributes to VSMC phenotypic transformation and proliferation in hypertension. Cell Death & Disease (2017).
4. Role of Vascular Smooth Muscle Cell Plasticity and Interactions in Vessel Wall Inflammation. Frontiers in Immunology (2020).
5. Inflammation and atherosclerosis: signaling pathways and therapeutic intervention. Signal Transduction and Targeted Therapy (2022).