Regulation of vascular smooth muscle cell apoptosis and cell senescence in atherosclerosis

Arteries clogged with fatty plaques are failing to repair themselves because their muscle cells are dying or going into a state of suspended animation instead of dividing to patch the damage. In healthy blood vessels, when smooth muscle cells die, neighbouring cells multiply to replace them—a process called apoptosis-induced compensatory proliferation (AICP). But in atherosclerosis, this repair mechanism stalls. The research will test whether cell senescence—a kind of cellular ageing—blocks AICP, and whether DNA damage from the cell’s nucleus or its mitochondria is the root cause. The team will also examine how damaged mitochondria trigger senescence in the first place. If the work identifies the DNA damage response or mitochondrial dysfunction as key drivers of plaque vulnerability, those pathways could become targets for new drugs. The goal is not to reverse advanced atherosclerosis overnight, but to stabilise dangerous plaques so they are less likely to rupture and cause heart attacks or strokes. This is fundamental science: it asks how cells decide to repair or retire, a question with implications far beyond heart disease. Similar mechanistic work on cell division and death has previously opened the door to cancer therapies and drugs that slow ageing.