Selenium supplementation improves antioxidant capacity in vitro and in vivo in patients with coronary artery disease: The SElenium Therapy in Coronary Artery disease Patients (SETCAP) Study.
Schnabel, Renate MD a,e; Lubos, Edith MD a,b,e; Messow, Claudia M. c; Sinning, Christoph R. MD a; Zeller, Tanja PhD a; Wild, Philipp S. MD a; Peetz, Dirk MD d; Handy, Diane E. PhD b; Munzel, Thomas MD, FAHA a; Loscalzo, Joseph MD, PhD b; Lackner, Karl J. MD d; Blankenberg, Stefan MD a
[Article]
American Heart Journal.
156(6):1201e1-1201e11, December 2008.
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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 [mu]g 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 [mu]g and from 38.1 U/gHb (33.2-43.8) to 42.6 U/gHb (35.0-49.1) (P < .0001) in the 500 [mu]g 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.
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