Such findings, considering the intricate vicious cycle between macrophage hepcidin autocrine-triggered iron retention and cholesterol disequilibrium, may shed new light on the "iron hypothesis" of atherosclerosis.
Increased serum hepcidin is associated with multiple types of cancer and atherosclerosis (AS), and therapeutics that decrease hepcidin levels have been proposed to treat these diseases.
Because hepcidin deficiency is associated with both increased serum iron and decreased macrophage iron, the possibility that increased serum iron was responsible for decreased atherosclerosis in Hamp<sup>-/-</sup>/ Ldlr<sup>-/-</sup> mice was considered.
Patients with hereditary hemochromatosis, despite extreme iron storage, do not show increased manifestation of atherosclerosis probably due to the low expression of hepcidin in macrophages.
Increased blood hepcidin may be associated with the presence and promotion of atherosclerosis, the association of hepcidin with mortality among coronary artery disease (CAD) patients remains unknown.
Increased body iron stores and hepcidin have been hypothesized to promote atherosclerosis by inducing macrophage iron accumulation and release of cytokines, but direct demonstration in human cells is lacking.
The proposed effects of hepcidin and iron in plaque progression offer an explanation of the paradox of no increase in atherosclerosis in patients with hemochromatosis despite a key role of iron in atherogenesis in normal subjects.