title: Efficacy of statins on sirtuin 1 and endothelial nitric oxide synthase expression: the role of sirtuin 1 gene variants in human coronary atherosclerosis.
abstract: Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and are used to reduce the risk of coronary artery disease (CAD) due to their pleiotropic effects. Recently, greater focus has been placed on the role of sirtuin 1 (SIRT1) in cardiovascular disease research. However, insufficient data exist on the relationships between statins, SIRT1 protein levels, and SIRT1 gene variants. In the present study, we investigated the effects of statins, atorvastatin and rosuvastatin, in CAD patients by analysing the associations between SIRT1 gene variants, rs7069102C>G and rs2273773C>T, and SIRT1/endothelial nitric oxide (eNOS) expression, as well as total antioxidant and oxidant status, and the oxidative stress index. SIRT1 expression was significantly higher, and eNOS expression was significantly lower in CAD patients when compared with controls. Statin treatment reduced SIRT1 expression and increased eNOS expression, similar to the levels found in the control population, independent from the studied SIRT1 gene variants. Oxidative stress parameters were significantly increased in CAD patients, and were decreased by statin treatment, demonstrating the antioxidative effects of statins on atherosclerosis. These results indicate that statin treatment could produce its protective effect on cardiovascular disease through the inhibition of SIRT1 expression. This is the first study reporting on the effect of statins, specifically atorvastatin and rosuvastatin, on SIRT1 expression in CAD patients.
authors.affiliation: Department of Medical Biology and Regenerative and Restorative Medicine Research Center (REMER), Istanbul Medipol University, Istanbul, Turkey.
authors.forename: Ulkan
authors.initials: U
authors.lastname: Kilic
authors.forename: Ozlem
authors.initials: O
authors.lastname: Gok
authors.forename: Birsen
authors.initials: B
authors.lastname: Elibol-Can
authors.forename: Omer
authors.initials: O
authors.lastname: Uysal
authors.forename: Ahmet
authors.initials: A
authors.lastname: Bacaksiz
mesh_terms: D000975:Antioxidants / Q000627:therapeutic use*; D000069059:Atorvastatin / Q000627:therapeutic use*; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D000068718:Rosuvastatin Calcium / Q000627:therapeutic use*; D056564:Sirtuin 1 / Q000235:genetics* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000068718:Rosuvastatin Calcium; D000069059:Atorvastatin; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: coronary artery disease; endothelial nitric oxide; oxidative stress; sirtuin 1 gene variant; statin