{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T09:18:25Z","timestamp":1777022305611,"version":"3.51.4"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,12,13]],"date-time":"2013-12-13T00:00:00Z","timestamp":1386892800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["HL14388"],"award-info":[{"award-number":["HL14388"]}]},{"DOI":"10.13039\/100000738","name":"US Department of Veterans Affairs","doi-asserted-by":"crossref","award":["1 I01 BX001414"],"award-info":[{"award-number":["1 I01 BX001414"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:title>New Findings<\/jats:title><jats:sec><jats:label\/><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p><jats:bold>What is the topic of this review?<\/jats:bold><\/jats:p>\n<jats:p>This symposium report summarizes autonomic, cardiac and skeletal muscle abnormalities in sarcoglycan\u2010\u03b4\u2010deficient mice (<jats:italic>Sgcd<\/jats:italic>\u2212\/\u2212), a mouse model of limb girdle muscular dystrophy, with emphasis on the roles of autonomic dysregulation and activation of the renin\u2013angiotensin system at a young age.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What advances does it highlight?<\/jats:bold><\/jats:p>\n<jats:p>The contributions of the autonomic nervous system and the renin\u2013angiotensin system to the pathogenesis of muscular dystrophy are highlighted. Results demonstrate that autonomic dysregulation precedes and predicts later development of cardiac dysfunction in <jats:italic>Sgcd<\/jats:italic>\u2212\/\u2212 mice and that treatment of young <jats:italic>Sgcd<\/jats:italic>\u2212\/\u2212 mice with the angiotensin type\u00a01 receptor antagonist losartan or with angiotensin\u2010(1\u20137) abrogates the autonomic dysregulation, attenuates skeletal muscle pathology and increases spontaneous locomotor activity.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>Muscular dystrophies are a heterogeneous group of genetic muscle diseases characterized by muscle weakness and atrophy. Mutations in sarcoglycans and other subunits of the dystrophin\u2013glycoprotein complex cause muscular dystrophy and dilated cardiomyopathy in animals and humans. Aberrant autonomic signalling is recognized in a variety of neuromuscular disorders. We hypothesized that activation of the renin\u2013angiotensin system contributes to skeletal muscle and autonomic dysfunction in mice deficient in the sarcoglycan\u2010\u03b4 (<jats:italic>Sgcd<\/jats:italic>) gene at a young age and that this early autonomic dysfunction contributes to the later development of left ventricular (LV) dysfunction and increased mortality. We demonstrated that young <jats:italic>Sgcd<\/jats:italic>\u2212\/\u2212 mice exhibit histopathological features of skeletal muscle dystrophy, decreased locomotor activity and severe autonomic dysregulation, but normal LV function. Autonomic regulation continued to deteriorate in <jats:italic>Sgcd<\/jats:italic>\u2212\/\u2212 mice with age and was accompanied by LV dysfunction and dilated cardiomyopathy at older ages. Autonomic dysregulation at a young age predicted later development of LV dysfunction and higher mortality in <jats:italic>Sgcd<\/jats:italic>\u2212\/\u2212 mice. Treatment of <jats:italic>Sgcd<\/jats:italic>\u2212\/\u2212 mice with the angiotensin type\u00a01 receptor blocker losartan for 8\u20139\u00a0weeks, beginning at 3\u00a0weeks of age, decreased fibrosis and oxidative stress in skeletal muscle, increased locomotor activity and prevented autonomic dysfunction. Chronic infusion of the counter\u2010regulatory peptide angiotensin\u2010(1\u20137) resulted in similar protection. We conclude that activation of the renin\u2013angiotensin system, at a young age, contributes to skeletal muscle and autonomic dysfunction in muscular dystrophy. We speculate that the latter is mediated via abnormal sensory nerve and\/or cytokine signalling from dystrophic skeletal muscle to the brain and contributes to age\u2010related LV dysfunction, dilated cardiomyopathy, arrhythmias and premature death. Therefore, correcting the early autonomic dysregulation and renin\u2013angiotensin system activation may provide a novel therapeutic approach in muscular dystrophy.<\/jats:p><\/jats:sec>","DOI":"10.1113\/expphysiol.2013.074336","type":"journal-article","created":{"date-parts":[[2013,12,14]],"date-time":"2013-12-14T03:57:12Z","timestamp":1386993432000},"page":"627-631","source":"Crossref","is-referenced-by-count":18,"title":["Autonomic, locomotor and cardiac abnormalities in a mouse model of muscular dystrophy: targeting the renin\u2013angiotensin system"],"prefix":"10.1113","volume":"99","author":[{"given":"Rasna","family":"Sabharwal","sequence":"first","affiliation":[{"name":"Department of Internal Medicine University of Iowa Carver College of Medicine  Iowa City IA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark W.","family":"Chapleau","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Iowa Carver College of 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