High Circulating Iron Levels Are a Risk Factor for Cardiovascular Disease: Clinical Implications for Iron-Overload Conditions

• Published in: Blood 2015-12, Vol.126 (23), p.1040-1040
• Main Authors: Vinchi, Francesca, Simmelbauer, Andreas, Costa da Silva, Milene, Altamura, Sandro, Galy, Bruno, Hentze, Matthias W., Muckenthaler, Martina U.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V126.23.1040.1040

Pathologies associated with increased circulating iron levels include primary iron overload disorders, such as hereditary hemochromatosis, as well as secondary iron overload disorders, such as thalassemia, sickle cell anemia and myelodysplastic syndromes. In the latter elevated circulating iron levels due to enhanced intestinal iron absorption in support of ineffective erythropoiesis are further increased by the need of chronic blood transfusions. Organ toxicity and increased patient mortality under these conditions are mainly attributed to iron overload and the occurrence of non-transferrin-bound iron (NTBI). So far, epidemiological data and studies in animal models have provided conflicting evidence regarding a role of excess iron in atherogenesis and thrombosis. Here we investigate the role of high circulating iron levels in the development of cardiovascular disease. A mouse model of type IV hereditary hemochromatosis, in which the hepcidin/ferroportin regulatory circuitry is disrupted due to a point mutation in the iron exporter ferroportin (Altamura et al., Cell Metabolism 2014), was interbred with ApoE-null mice, to study its susceptibility to atherosclerosis. As expected, this novel mouse model shows close to 100% transferrin saturation as well as NTBI. The mice were studied at 3, 6 and 12 months of age. We observed a mildly decreased lesion size and number at 3 months of age (6.15±1.25 vs 1.84±0.86 % aortic lesion area, P=0.02), while the same parameters were strongly increased in 6 to 12 month-old mice (6 months: 1.44±0.23 vs 5±0.53 % aortic lesion area, P=0.0001; 12 months: 10.24±1.21 vs 20.44±2.69 % aortic lesion area, P=0.0065). The atherosclerotic phenotype positively correlates with higher levels of circulating iron (12 months: 122.2±6.57 vs 337±19.22 mg iron/dl serum, P