Abstract: Increased atrial oxidative stress has an important role in inducing and maintaining atrial fibrillation (AF), and the activation of the small GTPase Rac1 contributes to the oxidative stress. We investigated the relationship of Rac1, atrial endothelial thromboprotective markers and AF inducibility and if simvastatin has a potential beneficial effect on a myocardial infarction (MI)-induced heart failure (HF) rat model. Rats were randomized into three groups (shams, MI group and simvastatin treatment group) and underwent echocardiography, AF induction studies and left atrial (LA) fibrosis analysis. Atrial Rac 1, sodium calcium exchanger (INCX), sarcoplasmic reticulum calcium ATPase (SERCA), endothelial nitric oxide synthase (eNOS) and induced nitric oxide synthase (iNOS) were measured. AF inducibility, AF duration and LA fibrosis were significantly higher in the MI group (p < 0.001 vs. sham), which were significantly reduced by simvastatin (p < 0.05 vs. MI). The reduced expressions of atrial eNOS, SERCA, thrombomodulin, tissue factor pathway inhibitor and tissue plasminogen activator in the MI group were significantly improved by simvastatin. Furthermore, the increased expression of atrial iNOS, INCX and Rac1 activity were significantly decreased by the simvastatin. Oxidative stress, endothelial dysfunction and thrombogenicity are associated with the promotion of AF in a rat model of ischemic HF. These were associated with increased Rac1 activity, and simvastatin treatment prevents these changes.
Keywords: statin; atrial fibrillation; nitric oxide synthase; heart failure
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Cho, K.-I.; Koo, S.-H.; Cha, T.-J.; Heo, J.-H.; Kim, H.-S.; Jo, G.-B.; Lee, J.-W. Simvastatin Attenuates the Oxidative Stress, Endothelial Thrombogenicity and the Inducibility of Atrial Fibrillation in a Rat Model of Ischemic Heart Failure. Int. J. Mol. Sci. 2014, 15, 14803-14818.
Cho K-I, Koo S-H, Cha T-J, Heo J-H, Kim H-S, Jo G-B, Lee J-W. Simvastatin Attenuates the Oxidative Stress, Endothelial Thrombogenicity and the Inducibility of Atrial Fibrillation in a Rat Model of Ischemic Heart Failure. International Journal of Molecular Sciences. 2014; 15(8):14803-14818.
Cho, Kyoung-Im; Koo, Sang-Ho; Cha, Tae-Joon; Heo, Jung-Ho; Kim, Hyun-Su; Jo, Gee-Bum; Lee, Jae-Woo. 2014. "Simvastatin Attenuates the Oxidative Stress, Endothelial Thrombogenicity and the Inducibility of Atrial Fibrillation in a Rat Model of Ischemic Heart Failure." Int. J. Mol. Sci. 15, no. 8: 14803-14818.