Statins initiated after hypertrophy inhibit oxidative stress and prevent heart failure in rats with aortic stenosis.
OBJECTIVE
Heart failure is a major and escalating public health problem. Recent studies have demonstrated that statins prevented chronic heart failure (CHF) in animal studies. However, it is unknown whether statins therapy initiated after left ventricular (LV) hypertrophy is evident can still effectively prevent CHF. This study tested the hypothesis that statins can prevent the transition of hypertrophy to heart failure.


RESULTS
The rats were studied at 6, 12, and 20 weeks after aortic stenosis (AS) operation. Some rats were given simvastatin (2.0 mg kg(-1) per day) from 13 weeks after AS operation for 8 weeks. Coarctation of aorta in rats resulted in compensatory LV hypertrophy (LVH), concomitant with an increase of superoxide levels and cardiomyocyte apoptosis in LV tissues at 12 weeks after AS operation. This was followed by CHF with a progressive increase in superoxide levels and cardiomyocyte apoptosis in LV tissues at 20 weeks after AS operation. Simvastatin treatment initiated from 13 weeks after AS operation significantly improved LV function and reduced superoxide levels and cardiomyocyte apoptosis in LV tissues. Pretreatment of simvastatin suppressed the hydrogen peroxide-induced apoptosis of cultured cardiomyocytes from neonatal rats.


CONCLUSIONS
These data indicate that long-term administration of simvastatin improved LV function and prevented the transition of hypertrophy to CHF. Inhibition of oxidative stress and cardiomyocyte apoptosis may contribute to the benefits of simvastatin treatment on heart of rats with AS.
Chen
Min-Sheng
MS
Department of Pharmacology, Guangzhou Medical College, Guangzhou 510182, China.
Xu
Fang-Ping
FP
Wang
Yan-Zhen
YZ
Zhang
Gui-Ping
GP
Yi
Quan
Q
Zhang
Hui-Qiu
HQ
Luo
Jian-Dong
JD
D000818:Animals; D001017:Aortic Coarctation / Q000150:complications; D001024:Aortic Valve Stenosis / Q000150:complications; D017209:Apoptosis / Q000187:drug effects; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis / Q000235:genetics; D002303:Cardiac Output, Low / Q000209:etiology / Q000517:prevention & control*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002908:Chronic Disease; D006352:Heart Ventricles / Q000166:cytology / Q000473:pathology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D013481:Superoxides / Q000032:analysis / Q000378:metabolism
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012333:RNA, Messenger; D013481:Superoxides; D009320:Atrial Natriuretic Factor; D019821:Simvastatin; D006861:Hydrogen Peroxide; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases