Iron accumulation drives atherosclerosis through oxidative stress and ferroptosis

Iron overload in arteries emerges as a silent catalyst for atherosclerosis, with researchers tracing how dysregulated iron metabolism generates a cascade of oxidative stress and ferroptosis-type cell death. When macrophages recycle iron from senescent red blood cells—a process amplified by intra-plaque hemorrhage—intracellular iron concentration rises, escalating oxidized LDL uptake, blocking cholesterol efflux, and accelerating foam cell formation, the hallmark of vulnerable plaque. This iron excess suppresses GPX4 expression, a critical antioxidant enzyme, unleashing reactive oxygen species and lipid peroxidation: a cascade of oxidative damage that impairs endothelial function and undermines plaque stability. While ferroptosis inhibition emerges as a compelling therapeutic target, researchers flag critical constraints: ferroptosis's role varies sharply between early and late disease phases, optimal intervention timing remains unclear, and systemic iron modulation carries risks of hepatotoxicity and cardiotoxicity. For the longevity-focused reader, this signals that before experimenting with iron chelators or natural ferroptosis modulators, the therapeutic window and safety profile remain unmapped territory.