title: Early dystrophin disruption in the pathogenesis of experimental chronic Chagas cardiomyopathy.
abstract: Chronic Chagas cardiomyopathy evolves over a long period of time after initial infection by Trypanosoma cruzi. Similarly, a cardiomyopathy appears later in life in muscular dystrophies. This study tested the hypothesis that dystrophin levels are decreased in the early stage of T. cruzi-infected mice that precedes the later development of a cardiomyopathy. CD1 mice were infected with T. cruzi (Brazil strain), killed at 30 and 100 days post infection (dpi), and the intensity of inflammation, percentage of interstitial fibrosis, and dystrophin levels evaluated. Echocardiography and magnetic resonance imaging data were evaluated from 15 to 100 dpi. At 30 dpi an intense acute myocarditis with ruptured or intact intracellular parasite nests was observed. At 100 dpi a mild chronic fibrosing myocarditis was detected without parasites in the myocardium. Dystrophin was focally reduced or completely lost in cardiomyocytes at 30 dpi, with the reduction maintained up to 100 dpi. Concurrently, ejection fraction was reduced and the right ventricle was dilated. These findings support the hypothesis that the initial parasitic infection-induced myocardial dystrophin reduction/loss, maintained over time, might be essential to the late development of a cardiomyopathy in mice.
authors.affiliation: Department of Pathology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, S.P., Brazil.
authors.forename: Cibele M
authors.initials: CM
authors.lastname: Prado
authors.forename: Mara R N
authors.initials: MR
authors.lastname: Celes
authors.forename: Lygia M
authors.initials: LM
authors.lastname: Malvestio
authors.forename: Erica C
authors.initials: EC
authors.lastname: Campos
authors.forename: João S
authors.initials: JS
authors.lastname: Silva
authors.forename: Linda A
authors.initials: LA
authors.lastname: Jelicks
authors.forename: Herbert B
authors.initials: HB
authors.lastname: Tanowitz
authors.forename: Marcos A
authors.initials: MA
authors.lastname: Rossi
mesh_terms: D000818:Animals; D002598:Chagas Cardiomyopathy / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D016189:Dystrophin / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009205:Myocarditis / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018512:Parasitemia / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D014349:Trypanosoma cruzi; D014463:Ultrasonography
chemical_list: D016189:Dystrophin