Role of endothelin 1 in the pathogenesis of chronic chagasic heart disease.
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.
Tanowitz
Herbert B
HB
Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA. tanowitz@aecom.yu.edu
Huang
Huan
H
Jelicks
Linda A
LA
Chandra
Madhulika
M
Loredo
Maria L
ML
Weiss
Louis M
LM
Factor
Stephen M
SM
Shtutin
Vitaliy
V
Mukherjee
Shankar
S
Kitsis
Richard N
RN
Christ
George J
GJ
Wittner
Murray
M
Shirani
Jamshid
J
Kisanuki
Yaz Y
YY
Yanagisawa
Masashi
M
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
D019332:Endothelin-1