Heart HealthHow Aging Macrophages Drive Plaque Buildup and New Ways to Stop Them
Atherosclerosis, the leading cause of death worldwide, is driven in large part by dysfunctional immune cells called macrophages. As macrophages age inside arterial plaques, they enter a state called senescence — becoming permanently growth-arrested and releasing inflammatory signals that destabilize plaques and impair the cleanup of dead cells. They also undergo various forms of programmed cell death, including pyroptosis and necroptosis, which enlarge the dangerous necrotic cores inside plaques. This review maps the shared molecular pathways governing both processes — including NF-κB, mTOR, and p53 — and highlights emerging therapies such as senolytics, NLRP3 inhibitors, and ferroptosis suppressors. Natural compounds like quercetin and melatonin are also examined for their ability to disrupt these harmful processes, pointing toward dual-targeted strategies for reducing cardiovascular disease risk.
