Smooth Muscle Cell Senescence Drives Atherosclerosis: New Therapeutic Targets Identified

This review in Cells examines how cellular senescence in vascular smooth muscle cells—not just cholesterol accumulation—actively drives atherosclerosis, the underlying cause of most heart attacks and strokes. Smooth muscle cells normally maintain arterial structure, but when they become senescent, they switch to a pro-inflammatory, calcifying phenotype that destabilizes plaques and promotes vessel stiffness. The review synthesizes evidence showing these senescent cells secrete harmful factors, recruit immune cells, and transform into foam cells that worsen plaque buildup. Importantly, it identifies specific molecular pathways driving this plasticity, potentially offering new drug targets. Unlike statins that only address cholesterol, interventions targeting smooth muscle senescence—through senolytics that clear senescent cells or drugs blocking their harmful transformations—could address a root cause of vascular aging. Given that cardiovascular disease remains the leading cause of death globally and worsens dramatically with age, understanding this mechanism matters enormously. Several senolytic drugs are already in human trials for other conditions, raising the possibility of repurposing them for atherosclerosis prevention in the relatively near term.