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Long‐term administration of pirfenidone improves cardiac function in mdx mice
Author(s) -
Van Erp Christel,
Irwin Nicole G.,
Hoey Andrew J.
Publication year - 2006
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.20590
Subject(s) - pirfenidone , medicine , duchenne muscular dystrophy , cardiac function curve , fibrosis , contractility , cardiac fibrosis , cardiomyopathy , endocrinology , myocardial fibrosis , muscular dystrophy , dystrophin , mdx mouse , antagonist , cardiology , heart failure , receptor , idiopathic pulmonary fibrosis , lung
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