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

van Erp, Christel and Irwin, Nicole G. and Hoey, Andrew J. (2006) Long-term administration of pirfenidone improves cardiac function in mdx mice. Muscle and Nerve, 34 (3). pp. 327-334. ISSN 0148-639X

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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 the cytokine, 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% of 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.

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Item Type:	Article (Commonwealth Reporting Category C)
Refereed:	Yes
Item Status:	Live Archive
Additional Information:	Deposited in accordance with the copyright policy of the publisher.
Faculty/School / Institute/Centre:	Historic - Faculty of Sciences - Department of Biological and Physical Sciences (Up to 30 Jun 2013)
Faculty/School / Institute/Centre:	Historic - Faculty of Sciences - Department of Biological and Physical Sciences (Up to 30 Jun 2013)
Date Deposited:	11 Oct 2007 01:13
Last Modified:	25 Sep 2013 02:22
Uncontrolled Keywords:	Duchenne muscular dystrophy; fibrosis; mdx mice; pirfenidone; TGF-β
Fields of Research (2008):	06 Biological Sciences > 0606 Physiology > 060699 Physiology not elsewhere classified 06 Biological Sciences > 0604 Genetics > 060412 Quantitative Genetics (incl. Disease and Trait Mapping Genetics) 11 Medical and Health Sciences > 1102 Cardiovascular Medicine and Haematology > 110201 Cardiology (incl. Cardiovascular Diseases)
Socio-Economic Objectives (2008):	E Expanding Knowledge > 97 Expanding Knowledge > 970111 Expanding Knowledge in the Medical and Health Sciences
Identification Number or DOI:	https://doi.org/10.1080/10641960600798754
URI:	http://eprints.usq.edu.au/id/eprint/2728

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