title: Role of endothelin 1 in the pathogenesis of chronic chagasic heart disease.
abstract: On the basis of previous observations, endothelin 1 (ET-1) has been suggested as contributing to the pathogenesis of Chagasic cardiomyopathy. Therefore, ET-1flox/flox;alpha-MHC-Cre(+) mice in which the ET-1 gene was deleted from cardiac myocytes and ET-1flox/flox;Tie 2 Cre(+) mice in which the ET-1 gene was deleted from endothelial cells were infected with Trypanosoma cruzi. Genetic controls for these cell-specific ET-1 knockout mice were used. Ninety percentage of all mice survived acute infection with the Brazil strain and were evaluated 130 days postinfection. Inflammation and fibrosis were observed in all infected mice; however, fibrosis was reduced in ET-1flox/flox;alpha-MHC-Cre(+) mice. Cardiac magnetic resonance imaging revealed that infection resulted in a significant increase in right ventricular internal diameter (RVID) in all mice except ET-1flox/flox;alpha-MHC-Cre(+) mice; i.e., RVID was not changed in infected ET-1flox/flox;alpha-MHC-Cre(+) mice. Echocardiography of the left ventricle demonstrated increased left ventricular end-diastolic diameter, reduced fractional shortening, and decreased relative wall thickness in infected mice. However, the magnitude of the changes was significantly less in ET-1flox/flox;alpha-MHC-Cre(+) mice compared to other groups. These data provide further evidence of a role for ET-1, particularly cardiac myocyte-derived ET-1, in the pathogenesis of chronic Chagasic cardiomyopathy.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA. tanowitz@aecom.yu.edu
authors.forename: Herbert B
authors.initials: HB
authors.lastname: Tanowitz
authors.forename: Huan
authors.initials: H
authors.lastname: Huang
authors.forename: Linda A
authors.initials: LA
authors.lastname: Jelicks
authors.forename: Madhulika
authors.initials: M
authors.lastname: Chandra
authors.forename: Maria L
authors.initials: ML
authors.lastname: Loredo
authors.forename: Louis M
authors.initials: LM
authors.lastname: Weiss
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Factor
authors.forename: Vitaliy
authors.initials: V
authors.lastname: Shtutin
authors.forename: Shankar
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Richard N
authors.initials: RN
authors.lastname: Kitsis
authors.forename: George J
authors.initials: GJ
authors.lastname: Christ
authors.forename: Murray
authors.initials: M
authors.lastname: Wittner
authors.forename: Jamshid
authors.initials: J
authors.lastname: Shirani
authors.forename: Yaz Y
authors.initials: YY
authors.lastname: Kisanuki
authors.forename: Masashi
authors.initials: M
authors.lastname: Yanagisawa
mesh_terms: D000818:Animals; D002598:Chagas Cardiomyopathy / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D002908:Chronic Disease; D004452:Echocardiography; D019332:Endothelin-1 / Q000235:genetics / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018512:Parasitemia / Q000401:mortality / Q000473:pathology
chemical_list: D019332:Endothelin-1