Hypothetical molecular mechanisms by which local iron overload facilitates the development of venous leg ulcers and multiple sclerosis lesions

Medical Hypotheses
M Simka, Z Rybak

Abstract

This paper presents a hypothetical model of role for iron in the development of venous leg ulcers and multiple sclerosis. Elevated concentrations of iron were found in the skin affected by venous hypertension and also in the areas of brain with multiple sclerosis lesions. Individuals with hemochromatosis gene (HFE) mutations: C282Y and H63D, which result in a less efficient transport of iron by macrophages, are characterized by an increased risk for venous leg ulcer and multiple sclerosis. Multiple sclerosis is a T cell-mediated disease, and T cells probably participate in the development of venous ulcers. This deleterious role of ferric ions could be related to the regulation of T cell proliferation and apoptosis. Under normal conditions excessive accumulation of T cells cannot take place, because nitric oxide and interferon-gamma drive these cells toward apoptosis. However, in tissues with a high concentration of iron, T lymphocytes proliferate instead of undergoing apoptosis. This is possible due to the internalization of the INF-gammaR2 chain of the interferon-gamma receptor, the downregulation of inducible nitric oxide synthase expression in macrophages and the inactivation of the active site of caspases. Yet, it should be...Continue Reading

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Citations

Jul 1, 2010·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·A BettencourtB M Silva
Sep 3, 2009·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Ajay Vikram Singh, Paolo Zamboni
Dec 5, 2009·Journal of Vascular Surgery·Donato GemmatiPaolo Zamboni
Feb 24, 2015·Journal of Tissue Viability·Teresa J KelechiMargie Prentice
Dec 2, 2010·The International Journal of Lower Extremity Wounds·Ajay V SinghPaolo Zamboni

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