title: Long-term administration of pirfenidone improves cardiac function in mdx mice.
abstract: 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-beta), is a likely mediator. This study tested whether the TGF-beta 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-beta 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-beta antagonist, pirfenidone, can improve cardiac function in mdx mice, potentially providing a new avenue for developing cardiac therapies for patients with Duchenne muscular dystrophy.
authors.affiliation: Centre for Systems Biology, Faculty of Sciences, University of Southern Queensland, Toowoomba, Queensland 4350, Australia.
authors.forename: Christel
authors.initials: C
authors.lastname: Van Erp
authors.forename: Nicole G
authors.initials: NG
authors.lastname: Irwin
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Hoey
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D005355:Fibrosis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009137:Muscular Dystrophy, Animal / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D011728:Pyridones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000235:genetics; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000209:etiology / Q000473:pathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011728:Pyridones; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C093844:pirfenidone