{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:21:58Z","timestamp":1790767318784,"version":"4.1.0"},"reference-count":58,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"21","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,11,5]]},"abstract":"\n Background<\/jats:title>\n \n Muscular dystrophy (\n MD<\/jats:styled-content>\n ) causes a progressive cardiomyopathy characterized by diffuse fibrosis, arrhythmia, heart failure, and early death. Activation of the thromboxane\u2010prostanoid receptor (\n TP<\/jats:styled-content>\n r) increases calcium transients in cardiomyocytes and is proarrhythmic and profibrotic. We hypothesized that\n TP<\/jats:styled-content>\n r activation contributes to the cardiac phenotype of\n MD<\/jats:styled-content>\n , and that\n TP<\/jats:styled-content>\n r antagonism would improve cardiac fibrosis and function in preclinical models of\n MD<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Three different mouse models of\n MD<\/jats:styled-content>\n (mdx\/utrn double knockout, second generation mdx\/\n mTR<\/jats:styled-content>\n double knockout, and delta\u2010sarcoglycan knockout) were given normal drinking water or water containing 25\u00a0mg\/kg per day of the\n TP<\/jats:styled-content>\n r antagonist ifetroban, beginning at weaning. After 6\u00a0months (10\u00a0weeks for mdx\/utrn double knockout), mice were evaluated for cardiac and skeletal muscle function before euthanization. There was a 100% survival rate of ifetroban\u2010treated mice to the predetermined end point, compared with 60%, 43%, and 90% for mdx\/utrn double knockout, mdx\/mTR double knockout, and delta\u2010sarcoglycan knockout mice, respectively.\n TP<\/jats:styled-content>\n r antagonism improved cardiac output in mdx\/utrn double knockout and mdx\/\n mTR<\/jats:styled-content>\n mice, and normalized fractional shortening, ejection fraction, and other parameters in delta\u2010sarcoglycan knockout mice. Cardiac fibrosis in delta\u2010sarcoglycan knockout was reduced with\n TP<\/jats:styled-content>\n r antagonism, which also normalized cardiac expression of claudin\u20105 and neuronal nitric oxide synthase proteins and multiple signature genes of Duchenne MD.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n TP<\/jats:styled-content>\n r antagonism reduced cardiomyopathy and spontaneous death in mouse models of Duchenne and limb\u2010girdle\n MD<\/jats:styled-content>\n . Based on these studies, ifetroban and other\n TP<\/jats:styled-content>\n r antagonists could be novel therapeutics for treatment of the cardiac phenotype in patients with\n MD<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.118.011902","type":"journal-article","created":{"date-parts":[[2019,10,30]],"date-time":"2019-10-30T09:00:29Z","timestamp":1572426029000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":18,"title":["Antagonism of the Thromboxane\u2010Prostanoid Receptor as a Potential Therapy for Cardiomyopathy of Muscular Dystrophy"],"prefix":"10.1161","volume":"8","author":[{"given":"James D.","family":"West","sequence":"first","affiliation":[{"name":"Division of Allergy, Pulmonary, and Critical Care Vanderbilt University Medical Center Nashville TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristi 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