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Iron, oxidative stress, and redox signaling in the cardiovascular system

Authors

  • Aurélie Gudjoncik,

    1. Laboratoire de Physiopathologie et Pharmacologie Cardio-métaboliques (LPPCM) Inserm UMR866, Facultés de Médecine et de Pharmacie, Université de Bourgogne, Dijon, France
    2. Service de Cardiologie CHU Bocage, Dijon, France
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  • Charles Guenancia,

    1. Laboratoire de Physiopathologie et Pharmacologie Cardio-métaboliques (LPPCM) Inserm UMR866, Facultés de Médecine et de Pharmacie, Université de Bourgogne, Dijon, France
    2. Service de Cardiologie CHU Bocage, Dijon, France
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  • Marianne Zeller,

    1. Laboratoire de Physiopathologie et Pharmacologie Cardio-métaboliques (LPPCM) Inserm UMR866, Facultés de Médecine et de Pharmacie, Université de Bourgogne, Dijon, France
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  • Yves Cottin,

    1. Laboratoire de Physiopathologie et Pharmacologie Cardio-métaboliques (LPPCM) Inserm UMR866, Facultés de Médecine et de Pharmacie, Université de Bourgogne, Dijon, France
    2. Service de Cardiologie CHU Bocage, Dijon, France
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  • Catherine Vergely,

    1. Laboratoire de Physiopathologie et Pharmacologie Cardio-métaboliques (LPPCM) Inserm UMR866, Facultés de Médecine et de Pharmacie, Université de Bourgogne, Dijon, France
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  • Luc Rochette

    Corresponding author
    1. Laboratoire de Physiopathologie et Pharmacologie Cardio-métaboliques (LPPCM) Inserm UMR866, Facultés de Médecine et de Pharmacie, Université de Bourgogne, Dijon, France
    • Correspondence: Dr. Luc Rochette, Laboratoire de Physiopathologie et Pharmacologie Cardio-métaboliques (LPPCM) Inserm UMR866, Facultés de Médecine et de Pharmacie, Université de Bourgogne, 7 Boulevard Jeanne d’Arc, 21033 Dijon, France

      E-mail: Luc.rochette@u-bourgogne.fr

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Abstract

The redox state of the cell is predominantly dependent on an iron redox couple and is maintained within strict physiological limits. Iron is an essential metal for hemoglobin synthesis in erythrocytes, for oxidation–reduction reactions, and for cellular proliferation. The maintenance of stable iron concentrations requires the coordinated regulation of iron transport into plasma from dietary sources in the duodenum, from recycled senescent red cells in macrophages, and from storage in hepatocytes. The absorption of dietary iron, which is present in heme or nonheme form, is carried out by mature villus enterocytes of the duodenum and proximal jejunum. Multiple physiological processes are involved in maintaining iron homeostasis. These include its storage at the intracellular and extracellular level. Control of iron balance in the whole organism requires communication between sites of uptake, utilization, and storage. Key protein transporters and the molecules that regulate their activities have been identified. In this field, ferritins and hepcidin are the major regulator proteins. A variety of transcription factors may be activated depending on the level of oxidative stress, leading to the expression of different genes. Major preclinical and clinical trials have shown advances in iron-chelation therapy for the treatment of iron-overload disease as well as cardiovascular and chronic inflammatory diseases.

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