alexa Interdependence of cardiac iron and calcium in a murine model of iron overload.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Clinical & Experimental Pharmacology

Author(s): OttoDuessel M, Brewer C, Wood JC

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Abstract Iron cardiomyopathy in ß-thalassemia major patients is associated with a vitamin D deficiency. Stores of 25-OH-D3 are markedly reduced, whereas the active metabolite, 1-25-(OH)-D3, is normal or increased. Interestingly, the ratio of 25-OH-D3 to 1-25-(OH)-D3 (a surrogate for parathyroid hormone [PTH]) is the strongest predictor of cardiac iron. Increased PTH and 1-25-OH-D3 levels have been shown to up-regulate L-type voltage-gated calcium channels (LVGCC), the putative channel for cardiac iron uptake. Therefore, we postulate that a vitamin D deficiency increases cardiac iron by altering LVGCC regulation. Hemojuvelin knockout mice were calcitriol treated, PTH treated, vitamin D-depleted, or untreated. Half of the animals in each group received the Ca(2+)-channel blocker verapamil. Mn(2+) was infused to determine LVGCC activity. Hearts and livers were harvested for iron, calcium, and manganese measurements as well as histology. Cardiac iron did not differ among the treatment groups; however, liver iron was increased in vitamin D-depleted animals (P < 0.0003). Cardiac iron levels did not correlate with manganese uptake but were proportional to cardiac calcium levels (r(2) = 0.6; P < 0.0001). Verapamil treatment reduced both cardiac (P < 0.02) and hepatic (P < 0.003) iron levels significantly by 34\% and 28\%, respectively. The association between cardiac iron and calcium levels was maintained after verapamil treatment (r(2) = 0.3; P < 0.008). Vitamin D depletion is associated with an increase in liver, but not cardiac, iron accumulation. Cardiac iron uptake was strongly correlated with cardiac calcium stores and was significantly attenuated by verapamil, suggesting that cardiac calcium and iron are related. Copyright © 2011 Mosby, Inc. All rights reserved.
This article was published in Transl Res and referenced in Journal of Clinical & Experimental Pharmacology

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