Long-term administration of pirfenidone improves cardiac function in mdx mice

• Published in: Muscle & nerve Vol. 34; no. 3; pp. 327 - 334
• Main Authors: Van Erp, Christel, Irwin, Nicole G., Hoey, Andrew J.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.09.2006; Wiley
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Biological and medical sciences; Cardiomyopathies - drug therapy; Cardiomyopathies - etiology; Cardiomyopathies - pathology; Disease Models, Animal; Diseases of striated muscles. Neuromuscular diseases; Duchenne muscular dystrophy; Fibrosis; Male; mdx mice; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Inbred mdx; Muscle; Muscular Dystrophy, Animal - complications; Muscular Dystrophy, Animal - drug therapy; Muscular Dystrophy, Animal - pathology; Muscular Dystrophy, Duchenne - complications; Muscular Dystrophy, Duchenne - drug therapy; Muscular Dystrophy, Duchenne - pathology; Myocardium - pathology; Neurology; Pharmacology. Drug treatments; pirfenidone; Pyridones - pharmacology; RNA, Messenger - analysis; TGF-β; Transforming Growth Factor beta - genetics; Ventricular Dysfunction, Left - drug therapy; Ventricular Dysfunction, Left - etiology; Ventricular Dysfunction, Left - pathology; Human; Neuromuscular diseases; Nervous system diseases; Cardiomyopathy; Rodentia; Contractility; Cytokine; Cardiovascular disease; Myocardial disease; Long term; Protein; Genetic disease; Vertebrata; Mammalia; Mouse; pirfenidone; Heart disease; Duchenne muscular dystrophy; Fibrosis; mdx mice; TGF-β; Degeneration; Muscle; Stiffness
• ISSN: 0148-639X; 1097-4598
• DOI: 10.1002/mus.20590

Duchenne muscular dystrophy, an X‐linked recessive neuromuscular disorder due to lack of the protein dystrophin, manifests as progressive muscle degeneration and cardiomyopathy with increased fibrosis. The exact mechanisms involved in fibrosis are unknown, but a cytokine, transforming growth factor‐beta (TGF‐β), is a likely mediator. This study tested whether the TGF‐β antagonist, pirfenidone, could reduce cardiac fibrosis. Eight‐month‐old mdx mice were treated for 7 months with 0.4%, 0.8%, and 1.2% pirfenidone in drinking water; untreated water was given to control mdx and C57 mice. Mice treated with 0.8% and 1.2% pirfendone had lowered cardiac TGF‐β mRNA and improved in vitro cardiac contractility (P < 0.05) to levels consistent with C57 mice, yet without a change in cardiac stiffness or fibrosis. These results show that the TGF‐β antagonist, pirfenidone, can improve cardiac function in mdx mice, potentially providing a new avenue for developing cardiac therapies for patients with Duchenne muscular dystrophy. Muscle Nerve, 2006