title: Simvastatin attenuates the oxidative stress, endothelial thrombogenicity and the inducibility of atrial fibrillation in a rat model of ischemic heart failure.
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.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kosin University College of Medicine, Busan 602702, Korea. kyoungim74@gmail.com.
authors.forename: Kyoung-Im
authors.initials: KI
authors.lastname: Cho
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kosin University College of Medicine, Busan 602702, Korea. paulkoo@hanmail.net.
authors.forename: Sang-Ho
authors.initials: SH
authors.lastname: Koo
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kosin University College of Medicine, Busan 602702, Korea. chatjn@gmail.com.
authors.forename: Tae-Joon
authors.initials: TJ
authors.lastname: Cha
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kosin University College of Medicine, Busan 602702, Korea. lduggymdc@gmail.com.
authors.forename: Jung-Ho
authors.initials: JH
authors.lastname: Heo
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kosin University College of Medicine, Busan 602702, Korea. libaek@gmail.com.
authors.forename: Hyun-Su
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kosin University College of Medicine, Busan 602702, Korea. kyoungim74@dreamwiz.com.
authors.forename: Gee-Bum
authors.initials: GB
authors.lastname: Jo
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kosin University College of Medicine, Busan 602702, Korea. jwlee@ns.kosinmed.or.kr.
authors.forename: Jae-Woo
authors.initials: JW
authors.lastname: Lee
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000378:metabolism; D015153:Blotting, Western; D004452:Echocardiography; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000627:therapeutic use*
chemical_list: D019821:Simvastatin; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III