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Myocardial iron homeostasis and hepcidin expression in a rat model of heart failure at different levels of dietary iron intake

Petrak, Jiri, Havlenova, Tereza, Krijt, Matyas, Behounek, Matej, Franekova, Janka, Cervenka, Ludek, Pluhacek, Tomas, Vyoral, Daniel, Melenovsky, Vojtech
Biochimica et biophysica acta 2019 v.1863 no.4 pp. 703-713
animal models, diet, gene expression, gene expression regulation, genes, heart, heart failure, hepcidin, homeostasis, iron, iron absorption, messenger RNA, nutrient deficiencies, patients, prognosis, rats
Up to 50% of patients with chronic heart failure (HF) have systemic iron deficiency, which contributes to symptoms and poor prognosis. Myocardial iron deficiency (MID) in HF patients has been recently documented, but its causes and consequences are unknown. The goal of our study was to address these questions in a well-defined rat HF model induced by volume overload due to aorto-caval fistula.Modulation of dietary iron content in a rat model of HF has been used to address how iron status affects cardiac iron levels, heart structure and function, and how the presence of HF affects cardiac expression of hepcidin and other iron-related genes.MID developed in the rat model of heart failure. Iron supplementation did not normalize the myocardial iron content; however, it improved survival of HF animals compared to animals fed diet with normal iron content. We observed marked upregulation of hepcidin mRNA expression in HF animals, which was not associated with systemic or cardiac iron levels but strongly correlated with markers and parameters of heart injury. Identical iron-independent pattern was observed for expression of several iron-related genes.MID is not caused by defective iron absorption or decreased systemic iron levels, but rather by intrinsic myocardial iron deregulation. Altered cardiac expression of hepcidin and other iron-related genes is driven by iron-independent stimuli in the failing heart.Understanding of the causes and consequences of MID is critical for finding strategies how to improve cardiac iron stores and in HF patients.