Smooth Muscle Cell Differentiation and Phenotypic Plasticity

Smooth muscle cells (SMCs) form the essential contractile layer of blood vessels and various hollow organs, where they regulate tone, pressure and peristaltic movements. In their differentiated or contractile state, SMCs display an ordered arrangement of actin–myosin filaments, low proliferative activity and expression of lineage markers such as smooth muscle α-actin and calponin. However, upon injury or exposure to cytokines and altered mechanical forces, these cells can adopt a synthetic phenotype characterised by enhanced proliferation, migration, extracellular matrix production and reduced contractile protein expression. This remarkable phenotypic plasticity underlies both physiological repair processes and the pathogenesis of vascular diseases such as atherosclerosis, restenosis and aneurysm formation. The transition between contractile and synthetic states is governed by a complex interplay of transcriptional regulators, epigenetic modifications, growth factors (for example platelet-derived growth factor and transforming growth factor-β), biomechanical cues (substrate stiffness, shear stress) and developmental origin. Understanding the molecular circuits that direct SMC differentiation and phenotype switching offers insight into vessel development, homeostasis and regeneration, and informs the design of novel therapeutic and tissue-engineering approaches aimed at vascular repair, disease modelling and drug discovery.

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Smooth Muscle Cell Differentiation and Phenotypic Plasticity publication trend

The graph below shows the total number of articles in smooth muscle cell differentiation and phenotypic plasticity across all publications each year (not limited to Nature Index journals).

Technical terms

Phenotypic plasticity: The capacity of SMCs to switch between contractile and synthetic states in response to environmental or molecular cues.

Contractile phenotype: Differentiated state characterised by organised actin–myosin bundles, low proliferation and high expression of smooth muscle-specific proteins.

Synthetic phenotype: Activated state marked by elevated proliferation, migration, extracellular matrix synthesis and reduced contractile marker expression.

Induced pluripotent stem cell (iPSC): Somatic cell reprogrammed to a pluripotent state, capable of differentiating into vascular SMCs under appropriate conditions.

Hydrogel: Water-rich polymer network used as a three-dimensional scaffold to mimic extracellular matrix mechanics and influence SMC differentiation.

References

1. Effect of Mechanical Stimuli on the Phenotypic Plasticity of Induced Pluripotent Stem-Cell-Derived Vascular Smooth Muscle Cells in a 3D Hydrogel. ACS Applied Bio Materials (2023).
2. DNA glycosylase Neil3 regulates vascular smooth muscle cell biology during atherosclerosis development. Atherosclerosis (2021).
3. Embryonic origins of human vascular smooth muscle cells: implications for in vitro modeling and clinical application. Cellular and Molecular Life Sciences (2014).