BEYOND CONTRACTILITY: PHENOTYPIC SWITCHING OF VASCULAR SMOOTH MUSCLE CELLS IN ATHEROSCLEROSIS

Area of Science:

• Cardiovascular Biology
• Vascular Cell Biology
• Atherosclerosis Research

Background:

• Atherosclerosis involves inflammation, lipid accumulation, and arterial wall remodeling.
• Vascular smooth muscle cells (VSMCs) are key cellular players in atherosclerotic plaque development.
• VSMCs exhibit remarkable phenotypic plasticity in response to vascular injury and stress.

Purpose of the Study:

• To review molecular mechanisms of VSMC phenotypic modulation in atherosclerosis.
• To highlight key regulators and signaling pathways involved in VSMC plasticity.
• To discuss the dual roles of VSMCs in plaque progression and stabilization.

Main Methods:

• Literature review of current knowledge on VSMC behavior in atherosclerosis.
• Summary of lineage-tracing studies on VSMC alternative phenotypes.
• Analysis of transcriptional regulators and signaling pathways (e.g., PDGF, TGF-β, KLF4, TCF21, non-coding RNAs).

Main Results:

• VSMCs undergo phenotypic modulation, losing contractile properties and gaining synthetic/migratory traits.
• VSMCs can adopt diverse phenotypes, including macrophage-like and osteogenic states.
• VSMCs contribute to plaque growth, calcification, and structural remodeling, but also fibrous cap formation.

Conclusions:

• VSMC phenotypic plasticity is central to atherosclerosis pathogenesis.
• Understanding VSMC modulation mechanisms is crucial for developing new therapies.
• Targeting VSMC plasticity may improve treatment strategies for atherosclerotic cardiovascular disease.