title: The effects of resveratrol and SIRT1 activation on dystrophic cardiomyopathy.
abstract: The muscular dystrophies, which cause progressive weakening of the skeletal muscles, are frequently associated with cardiomyopathy. In fact, the leading cause of mortality in patients with Duchenne muscular dystrophy, the most common and most severe type of muscular dystrophy, is heart failure due to cardiomyopathy. Therefore, more effective methods for treating cardiomyopathy are expected to improve long-term outcomes for patients with Duchenne muscular dystrophy. Our recent preclinical data show that treatment with the SIRT1 activator resveratrol is beneficial for dystrophic cardiomyopathy. We examined the effects of resveratrol treatment in two different models of muscular dystrophy: dystrophin-deficient mdx mice and δ-sarcoglycan-deficient TO-2 hamsters. In both models, resveratrol suppressed cardiac hypertrophy, preserved cardiac function, and reduced tissue fibrosis in the diseased heart. Importantly, resveratrol significantly improved survival in TO-2 hamsters. Resveratrol also attenuated skeletal muscle pathology in mdx mice. These promising results indicate resveratrol's potential for clinical translation to treat cardiomyopathy in patients with muscular dystrophies.
authors.affiliation: Department of Pharmacology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kuno
authors.affiliation: Department of Cardiovascular, Renal, and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Tanno
authors.affiliation: Department of Pharmacology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Horio
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000201:enzymology; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000201:enzymology; D059748:Proteolysis; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D054875:Ubiquitination
chemical_list: D002316:Cardiotonic Agents; D013267:Stilbenes; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000077185:Resveratrol
keywords: TO-2 hamster; dystrophic cardiomyopathy; mdx mouse; resveratrol