Table 1.

Iron and Atherosclerosis: In vitro and Animal Studies

Reference	Cell/Material/Model	Relevant Findings	Comments
Nemeth E et al. 2004	Human embryonic kidney 293 cells expressing mouse ferroportin	Hepcidin binding causes fpn to be internalized/degraded, with decreased export of cellular iron	As ferroportin is expressed on the surface of macrophages, this work supports hepcidin’s role in intra-macrophage iron accrual
Chang C et al. 2013	Hep G2 cells (produce hepcidin)	Hepcidin mRNA expression was reduced by simvastatin	This dose-dependent effect supports an iron regulatory pathway-mediated pleotropic effect of statin
Ludwiczek S et al. 2003	Human monocyte lines (THP-1 and U937)	Ferroportin mRNA expression down-regulated by interferon- gamma and lipopolysaccharide	Supports mechanistic links between inflammation and human monocyte iron uptake
Satchell L and Leake DS. 2012	Isolated human LDL	Iron at pH 4.5 and 37°C (as in lysosomes) oxidized LDL	Lysosomal iron is a candidate for catalyzing LDL oxidation, a key step in atheroma formation; most labile iron in cells resides in lysosomes
Saeed O et al. 2013	Apolipoprotein E knockout mice	Suppression of hepcidin increased cholesterol efflux from macrophages, decreased foam cell formation and decreased plaque area	Showing the potential benefits of pharmacological manipulation of iron homeostasis in an atheroma-prone animal supports this as an anti-atherosclerosis therapeutic approach
Rajendran R et al. 2012	Cholesterol-fed New Zealand White (NZW) rabbits	Inverse correlation of spatial distribution of iron vs. calcium in atherosclerotic lesions	Intraplaque iron and atheroma are associated; speculations are drawn regarding iron accelerating vs. calcium attenuating plaque instability
Minqin R et al. 2005	Cholesterol-fed NZW rabbits	Reduced atheroma lesion size vs. controls	Preclinical data supporting potential efficacy of chelator in early atheroma development
Nagy E et al. 2010	Human atheroma, red blood cells and endothelial cells	Heme iron promotes and inhibition of heme release suppresses lipid oxidation, endothelial cytotoxicity	In vitro experiments supporting role of iron in human atheroma lipid oxidation and potential to attenuate atherogenesis by targeting heme iron
Moreno P et al. 2008	Human atheroma, haptoglobin (Hp) genotype	Hp 2-2 genotype predicted greater intraplaque iron in diabetics	Genetic factors associated with impaired iron clearance may help explain greater atherosclerosis burden in diabetes