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Am Heart J ; 156(6): 1201.e1-11, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19033020

ABSTRACT

BACKGROUND: Selenium is a central determinant of antioxidative glutathione peroxidase 1 (GPx-1) expression and activity. The relevance of selenium supplementation on GPx-1 in coronary artery disease (CAD) needs to be established. We assessed the effect of selenium supplementation on GPx-1 in cell culture and on endothelial function in a prospective clinical trial. METHODS: Human coronary artery endothelial cells were incubated with 5.78 to 578 nmol/L sodium selenite, Se-methyl-selenocysteine hydrochloride, or seleno-l-methionine. Glutathione peroxidase 1 mRNA and protein expression and activity were measured. Coronary artery disease patients (n = 465) with impaired endothelial function (flow-mediated dilation [FMD] <8%) were randomly assigned to receive 200 or 500 microg sodium selenite daily or matching placebo during a 12-week period. We tested the effect on red blood cell GPx-1 activity and brachial artery FMD. Furthermore, differences in biomarkers of oxidative stress and inflammation were measured. RESULTS: Sodium selenite and Se-methyl-selenocysteine hydrochloride increased GPx-1 protein and activity in a dose-dependent manner (P < .0001). The intention-to-treat groups comprised 433 CAD patients. Glutathione peroxidase 1 activity increased from 37.0 U/gHb (31.3-41.7) to 41.1 U/gHb (35.2-48.4) (P < .0001) in the 200 microg and from 38.1 U/gHb (33.2-43.8) to 42.6 U/gHb (35.0-49.1) (P < .0001) in the 500 microg sodium selenite group treated for 12-weeks. No relevant changes were observed for FMD or biomarkers of oxidative stress and inflammation. CONCLUSIONS: Sodium selenite supplementation increases GPx-1 activity in endothelial cells and in CAD patients. Future studies have to demonstrate whether long-term CAD outcome can be improved.


Subject(s)
Antioxidants/administration & dosage , Coronary Artery Disease/drug therapy , Cysteine/analogs & derivatives , Glutathione Peroxidase/blood , Organoselenium Compounds/administration & dosage , Selenomethionine/administration & dosage , Sodium Selenite/administration & dosage , Aged , Coronary Artery Disease/enzymology , Coronary Vessels/drug effects , Coronary Vessels/enzymology , Cysteine/administration & dosage , Dose-Response Relationship, Drug , Endothelium, Vascular/drug effects , Endothelium, Vascular/enzymology , Erythrocytes/enzymology , Female , Humans , In Vitro Techniques , Male , Middle Aged , Prospective Studies , Selenocysteine/analogs & derivatives , Vasodilation/drug effects
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