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.