Iron and atherosclerosis: Lessons learned from rabbits relevant to human disease

The role of iron in promoting atherosclerosis, and hence the cardiovascular, neurodegenerative and other diseases that result from atherosclerosis, has been fiercely controversial. Many studies have been carried out on various rodent models of atherosclerosis, especially on apoE-knockout (apoE^-/-) mice, which develop atherosclerosis more readily than normal mice. These apoE^-/- mouse studies generally support a role for iron in atherosclerosis development, although there are conflicting results. The purpose of the current article is to describe studies on another animal model that is not genetically manipulated; New Zealand White (NZW) rabbits fed a high-cholesterol diet. This may be a better model than the apoE^-/- mice for human atherosclerosis, although it has been given much less attention. Studies on NZW rabbits support the view that iron promotes atherosclerosis, although some uncertainties remain, which need to be resolved by further experimentation.