Causes, consequences and therapeutic potential of cell senescence in atherosclerosis (renewal)

Atherosclerotic plaques become dangerous when their protective fibrous caps thin and rupture, and this project targets the senescent smooth muscle cells that fail to maintain that cap. Heart attacks and strokes happen when advanced plaques destabilise. The fibrous cap that keeps plaques intact is built by vascular smooth muscle cells (VSMCs), but in advanced disease these cells stop dividing, enter a state called senescence, and die. Senescent cells also drive inflammation, making plaques even more unstable. Normally the immune system clears senescent cells, but in atherosclerosis this clearance fails. This project will investigate why VSMCs become senescent, how they evade clearance, and whether two drug classes—new to this context—can eliminate them or restore their function. If the research succeeds, it could lead to therapies that stabilise plaques before they rupture, preventing heart attacks and strokes without invasive procedures. This would directly affect the millions of people living with advanced atherosclerosis. The work is primarily fundamental science—understanding the cellular mechanisms of senescence and immune clearance in human tissue and mouse models—but it tests specific drugs with clear therapeutic potential, bridging basic discovery and clinical application.