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      Selenium and Its Supplementation in Cardiovascular Disease—What do We Know?

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          Abstract

          The trace element selenium is of high importance for many of the body’s regulatory and metabolic functions. Balanced selenium levels are essential, whereas dysregulation can cause harm. A rapidly increasing number of studies characterizes the wide range of selenium dependent functions in the human body and elucidates the complex and multiple physiological and pathophysiological interactions of selenium and selenoproteins. For the majority of selenium dependent enzymes, several biological functions have already been identified, like regulation of the inflammatory response, antioxidant properties and the proliferation/differentiation of immune cells. Although the potential role of selenium in the development and progression of cardiovascular disease has been investigated for decades, both observational and interventional studies of selenium supplementation remain inconclusive and are considered in this review. This review covers current knowledge of the role of selenium and selenoproteins in the human body and its functional role in the cardiovascular system. The relationships between selenium intake/status and various health outcomes, in particular cardiomyopathy, myocardial ischemia/infarction and reperfusion injury are reviewed. We describe, in depth, selenium as a biomarker in coronary heart disease and highlight the significance of selenium supplementation for patients undergoing cardiac surgery.

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          Most cited references104

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          Glutathione peroxidases.

          With increasing evidence that hydroperoxides are not only toxic but rather exert essential physiological functions, also hydroperoxide removing enzymes have to be re-viewed. In mammals, the peroxidases inter alia comprise the 8 glutathione peroxidases (GPx1-GPx8) so far identified. Since GPxs have recently been reviewed under various aspects, we here focus on novel findings considering their diverse physiological roles exceeding an antioxidant activity. GPxs are involved in balancing the H2O2 homeostasis in signalling cascades, e.g. in the insulin signalling pathway by GPx1; GPx2 plays a dual role in carcinogenesis depending on the mode of initiation and cancer stage; GPx3 is membrane associated possibly explaining a peroxidatic function despite low plasma concentrations of GSH; GPx4 has novel roles in the regulation of apoptosis and, together with GPx5, in male fertility. Functions of GPx6 are still unknown, and the proposed involvement of GPx7 and GPx8 in protein folding awaits elucidation. Collectively, selenium-containing GPxs (GPx1-4 and 6) as well as their non-selenium congeners (GPx5, 7 and 8) became key players in important biological contexts far beyond the detoxification of hydroperoxides. This article is part of a Special Issue entitled Cellular functions of glutathione. Copyright © 2012 Elsevier B.V. All rights reserved.
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            Selenium: biochemical role as a component of glutathione peroxidase.

            When hemolyzates from erythrocytes of selenium-deficient rats were incubated in vitro in the presence of ascorbate or H(2)O(2), added glutathione failed to protect the hemoglobin from oxidative damage. This occurred because the erythrocytes were practically devoid of glutathione-peroxidase activity. Extensively purified preparations of glutathione peroxidase contained a large part of the (75)Se of erythrocytes labeled in vivo. Many of the nutritional effects of selenium can be explained by its role in glutathione peroxidase.
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              Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases.

              The goal of this review is to place the exciting advances that have occurred in our understanding of the molecular biology of the types 1, 2, and 3 (D1, D2, and D3, respectively) iodothyronine deiodinases into a biochemical and physiological context. We review new data regarding the mechanism of selenoprotein synthesis, the molecular and cellular biological properties of the individual deiodinases, including gene structure, mRNA and protein characteristics, tissue distribution, subcellular localization and topology, enzymatic properties, structure-activity relationships, and regulation of synthesis, inactivation, and degradation. These provide the background for a discussion of their role in thyroid physiology in humans and other vertebrates, including evidence that D2 plays a significant role in human plasma T(3) production. We discuss the pathological role of D3 overexpression causing "consumptive hypothyroidism" as well as our current understanding of the pathophysiology of iodothyronine deiodination during illness and amiodarone therapy. Finally, we review the new insights from analysis of mice with targeted disruption of the Dio2 gene and overexpression of D2 in the myocardium.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                27 April 2015
                May 2015
                : 7
                : 5
                : 3094-3118
                Affiliations
                [1 ]Department of Thoracic and Cardiovascular Surgery, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany, E-Mails: agoetzenich@ 123456ukaachen.de (A.G.), skraemer@ 123456ukaachen.de (S.K.); sborosch@ 123456ukaachen.de (S.B.)
                [2 ]Department of Critical Care, Intensive Care Unit, Faculty of Medicine, Universidad de la República (UdeLaR), Italia Av. 14th floor. 11.600, Montevideo, Uruguay; E-Mail: wmanzanares@ 123456adinet.com.uy
                [3 ]Clinical Nutrition, College of Health, Massey University, Albany Campus Private Bag 102 904 Auckland 0632, New Zealand; E-Mail: g.hardy@ 123456massey.ac.nz
                [4 ]Institute of Biochemistry and Molecular Cell Biology, RWTH Aachen University, 52074 Aachen, Germany
                [5 ]Department of Anesthesiology, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany
                Author notes
                [†]

                These authors contributed equally to this work.

                [* ]Authors to whom correspondence should be addressed; E-Mails: cbenstoem@ 123456ukaachen.de (C.B.); christian.stoppe@ 123456gmail.com (C.S.); Tel.: +49-241-80-89386 (C.B.); +49-241-8036567 (C.S.); Fax: +49-241-80-82570 (C.B.); +49-241-802406 (C.S.).
                Article
                nutrients-07-03094
                10.3390/nu7053094
                4446741
                25923656
                1b5729dc-6428-4b0b-8126-09d187f0ba6c
                © 2015 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 28 February 2015
                : 16 April 2015
                Categories
                Review

                Nutrition & Dietetics
                cardiovascular disease,coronary heart disease,cardiac surgery,selenium selenoproteins

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