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Title : NON CHOLESTEROL LOWERING DOSE OF ATORVASTATIN AMELIORATES DIABETIC VENTRICULAR MYOCYTE DYSFUNCTION IN MICE
Authors : Gulgun Ozansoy, Aslı Ceylan-Isık, Fugen Aktan, Ahmet Cumaoglu, Aysel Arıcıoglu, Cimen Karasu, Nuray Arı
Abstract : The aim of this study was to investigate whether atorvastatin ameliorates diabetes-induced cardiomyocyte dysfunction, independently of cholesterol-lowering effect. Streptozotocin-induced diabetic mice were treated with atorvastatin (10 mg/kg, daily, orally) for two weeks. Ventricular cardiomyocytes were isolated and contractile properties including peak shortening (PS), time to PS (TPS), time to 90% relengthening (TR90) and maximal velocity of shortening/relengthening (+/- dL/dt) were analysed using video-based edge detection. Diabetes caused mechanical dysfunction with dampened stress tolerance of myocytes at high stress frequencies, all of which were significantly alleviated by atorvastatin without affecting hyperglycemia and dyslipidemia. In addition, changes in oxidative stress parameters (CAT activity, GSH and MDA levels) were also normalized by atorvastatin. These data indicate that atorvastatin, independently of its lipid-lowering capacity, reduces myocardial oxidative stress resulting in improved myocyte mechanical function in an experimental model of diabetes. Our results supports the concept that restriction of myocardial oxidative stress is a fundamental goal in the treatment of diabetic cardiomyopathy.

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