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Efficacy of statins on sirtuin 1 and endothelial nitric oxide synthase expression: the role of sirtuin 1 gene variants in human coronary atherosclerosis
Author(s) -
Kilic Ulkan,
Gok Ozlem,
ElibolCan Birsen,
Uysal Omer,
Bacaksiz Ahmet
Publication year - 2015
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12362
Subject(s) - rosuvastatin , sirtuin 1 , enos , atorvastatin , statin , oxidative stress , nitric oxide , coronary artery disease , medicine , endocrinology , resveratrol , pharmacology , nitric oxide synthase , biology , downregulation and upregulation , gene , biochemistry
Summary 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 ( SIRT 1) in cardiovascular disease research. However, insufficient data exist on the relationships between statins, SIRT 1 protein levels, and SIRT 1 gene variants. In the present study, we investigated the effects of statins, atorvastatin and rosuvastatin, in CAD patients by analysing the associations between SIRT 1 gene variants, rs7069102C>G and rs2273773C>T, and SIRT 1/endothelial nitric oxide ( eNOS ) expression, as well as total antioxidant and oxidant status, and the oxidative stress index. SIRT 1 expression was significantly higher, and eNOS expression was significantly lower in CAD patients when compared with controls. Statin treatment reduced SIRT 1 expression and increased eNOS expression, similar to the levels found in the control population, independent from the studied SIRT 1 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 SIRT 1 expression. This is the first study reporting on the effect of statins, specifically atorvastatin and rosuvastatin, on SIRT 1 expression in CAD patients.