August 12th, 2026
Iron metabolism is strongly connected to oxidative stress, the excessive production of reactive oxygen species and other oxidative molecules that outpaces the ability of cells to avoid, resist, or repair the consequent damage. It can lead to a form of programmed cell death called ferroptosis. Here, researchers describe how iron metabolism and ferroptosis are seen to contribute to the development of atherosclerosis. This isn't a very well developed area of research into cardiovascular disease, in that while one can paint an interesting mechanistic picture at the high level, much of the detail remains to be filled in, and robust forms of therapy based on manipulation of iron metabolism or ferroptosis have yet to emerge.
Disturbances in iron homeostasis have a bidirectional impact on the development of atherosclerosis. The classic "iron hypothesis" states that systemic iron overload increases the risk of cardiovascular diseases (CVDs), while controlling iron deficiency can protect blood vessels. Histopathological studies have confirmed that atherosclerotic plaques have a higher iron deposition compared to healthy blood vessels, and this phenomenon can be observed from the early stages of atherosclerosis. Macrophages recycle iron from senescent red blood cells, and intra-plaque hemorrhage exacerbates the phagocytosis of red blood cells, which is considered a key mechanism for iron deposition.
