Role of iron in atherosclerosis.

The importance of iron in injury is derived from the ease with which iron is reversibly oxidized and reduced and thus able to participate in the generation of powerful oxidant species, such as hydroxyl radical, and in lipid peroxidation. There is compelling mechanistic evidence for the potential role of iron in atherosclerosis: the role of iron in oxidizing low-density lipoprotein (LDL), iron chelators prevent endothelial cell damage by oxidized LDL, the ability of iron to cause endothelial cell damage, and iron chelators prevent endothelial cell dysfunction and vascular smooth muscle proliferation. In addition to these effects, important in atherosclerosis, ample experimental evidence suggests a role of iron in myocardial reperfusion injury. Epidemiological data have provided conflicting results, with several studies reporting an association between iron stores and progression of carotid atherosclerosis or acute myocardial infarction, whereas others argue against such an association. However, the availability of catalytic iron and the susceptibility of an individual may be more important than overall iron body status. Studies that address these issues, as well as those designed to establish cause and effect, are needed before one can reach meaningful conclusions about the role of iron in atherosclerosis and the therapeutic implications for patients.