Chronic Losartan Administration Reduces Mortality and Preserves Cardiac but Not Skeletal Muscle Function in Dystrophic Mice

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dc.contributor.authorBish, Lawrence T
dc.contributor.authorSleeper, Margaret M
dc.contributor.authorBish, Lawrence T
dc.contributor.authorYarchoan, Mark
dc.contributor.authorBarton, Elisabeth R
dc.contributor.authorSweeney, H. Lee
dc.contributor.authorMorine, Kevin J
dc.contributor.authorAcosta, Pedro
dc.contributor.authorBarton, Elisabeth R
dc.contributor.authorSweeney, H. Lee
dc.date2023-05-17T07:55:11.000
dc.date.accessioned2023-05-23T04:44:42Z
dc.date.available2023-05-23T04:44:42Z
dc.date.issued2011-06-22
dc.date.submitted2013-07-25T11:24:35-07:00
dc.description.abstractDuchenne muscular dystrophy (DMD) is a degenerative disorder affecting skeletal and cardiac muscle for which there is no effective therapy. Angiotension receptor blockade (ARB) has excellent therapeutic potential in DMD based on recent data demonstrating attenuation of skeletal muscle disease progression during 6–9 months of therapy in the mdx mouse model of DMD. Since cardiac-related death is major cause of mortality in DMD, it is important to evaluate the effect of any novel treatment on the heart. Therefore, we evaluated the long-term impact of ARB on both the skeletal muscle and cardiac phenotype of the mdx mouse. Mdx mice received either losartan (0.6 g/L) (n = 8) or standard drinking water (n = 9) for two years, after which echocardiography was performed to assess cardiac function. Skeletal muscle weight, morphology, and function were assessed. Fibrosis was evaluated in the diaphragm and heart by Trichrome stain and by determination of tissue hydroxyproline content. By the study endpoint, 88% of treated mice were alive compared to only 44% of untreated (p = 0.05). No difference in skeletal muscle morphology, function, or fibrosis was noted in losartan-treated animals. Cardiac function was significantly preserved with losartan treatment, with a trend towards reduction in cardiac fibrosis. We saw no impact on the skeletal muscle disease progression, suggesting that other pathways that trigger fibrosis dominate over angiotensin II in skeletal muscle long term, unlike the situation in the heart. Our study suggests that ARB may be an important prophylactic treatment for DMD-associated cardiomyopathy, but will not impact skeletal muscle disease.
dc.identifier.urihttps://repository.upenn.edu/handle/20.500.14332/48901
dc.legacy.articleid1013
dc.legacy.fieldstrue
dc.legacy.fields10.1371/journal.pone.0020856
dc.legacy.fulltexturlhttps://repository.upenn.edu/cgi/viewcontent.cgi?article=1013&context=vet_papers&unstamped=1
dc.rights© 2011 Bish et al. This is an open-access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by/3.0/">Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.source.beginpagee20856
dc.source.issue14
dc.source.issue6
dc.source.journalDepartmental Papers (Vet)
dc.source.journaltitlePLoS One
dc.source.peerreviewedtrue
dc.source.statuspublished
dc.source.volume6
dc.subject.otherCardiovascular Diseases
dc.subject.otherComparative and Laboratory Animal Medicine
dc.subject.otherMedicine and Health Sciences
dc.subject.otherMusculoskeletal Diseases
dc.titleChronic Losartan Administration Reduces Mortality and Preserves Cardiac but Not Skeletal Muscle Function in Dystrophic Mice
dc.typeArticle
digcom.contributor.authorisAuthorOfPublication|email:bish@mail.med.upenn.edu|institution:University of Pennsylvania|Bish, Lawrence T
digcom.contributor.authorYarchoan, Mark
digcom.contributor.authorisAuthorOfPublication|email:sleeper@vet.upenn.edu|institution:University of Pennsylvania|Sleeper, Margaret M
digcom.contributor.authorGazzara, Jeffrey
digcom.contributor.authorMorine, Kevin J
digcom.contributor.authorAcosta, Pedro
digcom.contributor.authorisAuthorOfPublication|email:erbarton@biochem.dental.upenn.edu|institution:University of Pennsylvania|Barton, Elisabeth R
digcom.contributor.authorisAuthorOfPublication|email:lsweeney@mail.med.upenn.edu|institution:University of Pennsylvania|Sweeney, H. Lee
digcom.identifiervet_papers/14
digcom.identifier.contextkey4347468
digcom.identifier.submissionpathvet_papers/14
digcom.typearticle
dspace.entity.typePublication
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upenn.schoolDepartmentCenterDepartmental Papers (Vet)
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