{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T14:07:37Z","timestamp":1740146857284,"version":"3.37.3"},"reference-count":27,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T00:00:00Z","timestamp":1706659200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["P24791059"],"award-info":[{"award-number":["P24791059"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014588","name":"Sanofi Pasteur","doi-asserted-by":"publisher","award":["GDC160982"],"award-info":[{"award-number":["GDC160982"]}],"id":[{"id":"10.13039\/100014588","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Background<\/jats:title><jats:p>Duchenne muscular dystrophy (DMD), a severe degenerative skeletal and cardiac muscle disease, has a poor prognosis, and no curative treatments are available. Because decreased autophagy has been reported to contribute to skeletal muscle degeneration, therapies targeting autophagy are expected to improve skeletal muscle hypofunction. However, the role of this regulatory mechanism has not been evaluated clearly in DMD cardiomyocytes.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Methods<\/jats:title><jats:p>In this present study, we evaluated myocardial fibrosis and its mechanism in<jats:italic>mdx<\/jats:italic>mice, a model of DMD, and also evaluated changes in cardiac function.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Results<\/jats:title><jats:p>As assessed by LC3 immunohistochemistry, a small number of autophagosomes were detected in cardiomyocytes of both<jats:italic>mdx<\/jats:italic>mice and control wild-type (WT) mice. The number of autophagosomes was significantly enhanced by 4 weeks of isoproterenol-induced cardiac stress in cardiomyocytes of<jats:italic>mdx<\/jats:italic>but not WT mice. Simultaneously, isoproterenol increased cardiomyocyte fibrosis in<jats:italic>mdx<\/jats:italic>but not WT mice. Administration of chloroquine significantly decreased cardiomyocyte fibrosis in<jats:italic>mdx<\/jats:italic>mice, even after isoproterenol treatment. Left ventricle size and function were evaluated by echocardiography. Left ventricular contraction was decreased in<jats:italic>mdx<\/jats:italic>mice after isoproterenol treatment compared with control mice, which was alleviated by chloroquine administration.<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Conclusions<\/jats:title><jats:p>Heart failure in DMD patients is possibly treated with chloroquine, and the mechanism probably involves chloroquine\u2019s anti-inflammatory effects.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0297083","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T18:35:49Z","timestamp":1706726149000},"page":"e0297083","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chloroquine decreases cardiac fibrosis and improves cardiac function in a mouse model of Duchenne muscular dystrophy"],"prefix":"10.1371","volume":"19","author":[{"given":"Takuya","family":"Hirata","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6253-6087","authenticated-orcid":true,"given":"Shiro","family":"Baba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kentaro","family":"Akagi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichi","family":"Matsuda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsutsugu","family":"Umeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Souichi","family":"Adachi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshio","family":"Heike","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junko","family":"Takita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,1,31]]},"reference":[{"issue":"2","key":"pone.0297083.ref001","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1002\/ajmg.1320290225","article-title":"A grandpaternally derived de novo deletion within Xp21 initially presenting in carrier females diagnosed as Kugelberg-Welander syndrome","volume":"29","author":"S Wood","year":"1988","journal-title":"Am J Med Genet"},{"issue":"6","key":"pone.0297083.ref002","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1136\/jmg.25.6.377","article-title":"Inherited deletion of subband Xp21.13 in a male with Duchenne muscular dystrophy","volume":"25","author":"W Werner","year":"1988","journal-title":"J Med Genet"},{"issue":"9307","key":"pone.0297083.ref003","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/S0140-6736(02)07815-7","article-title":"The muscular dystrophies.","volume":"359","author":"AE Emery","year":"2002","journal-title":"Lancet"},{"issue":"8014","key":"pone.0297083.ref004","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/S0140-6736(77)92211-5","article-title":"Frequency of Duchenne muscular dystrophy carriers","volume":"1","author":"M Zatz","year":"1977","journal-title":"Lancet"},{"key":"pone.0297083.ref005","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1136\/jnnp.2008.158329","article-title":"Diagnosis and new treatments in muscular dystrophies","volume":"80","author":"AYY Manzur","year":"2009","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"pone.0297083.ref006","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/0140-6736(91)91432-T","article-title":"Mode of death in Duchenne muscular dystrophy","volume":"337","author":"V Patterson","year":"1991","journal-title":"Lancet"},{"key":"pone.0297083.ref007","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0022-510X(87)90092-X","article-title":"Life spans of Duchenne muscular dystrophy patients in the hospital care program in Japan","volume":"81","author":"M Mukoyama","year":"1987","journal-title":"J Neurol Sci"},{"key":"pone.0297083.ref008","first-page":"207","volume-title":"Management. 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