Role of endothelin 1 in the pathogenesis of chronic chagasic heart disease

Herbert B. Tanowitz, Huan Huang, Linda A. Jelicks, Madhulika Chandra, Maria L. Loredo, Louis M. Weiss, Stephen M. Factor, Vitaliy Shtutin, Shankar Mukherjee, Richard N. Kitsis, George J. Christ, Murray Wittner, Jamshid Shirani, Yaz Y. Kisanuki, Masashi Yanagisawa

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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;α-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;α-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-1 flox/flox; α-MHC-Cre(+) mice; i.e., RVID was not changed in infected ET-1flox/flox;α-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;α-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.

Original languageEnglish (US)
Pages (from-to)2496-2503
Number of pages8
JournalInfection and Immunity
Volume73
Issue number4
DOIs
StatePublished - Apr 2005

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Endothelin-1
Heart Diseases
Cardiomyopathies
Cardiac Myocytes
Fibrosis
Trypanosoma cruzi
Infection
Knockout Mice
Genes
Heart Ventricles
Brazil
Echocardiography
Endothelial Cells
Magnetic Resonance Imaging
Inflammation

ASJC Scopus subject areas

  • Immunology

Cite this

Tanowitz, H. B., Huang, H., Jelicks, L. A., Chandra, M., Loredo, M. L., Weiss, L. M., ... Yanagisawa, M. (2005). Role of endothelin 1 in the pathogenesis of chronic chagasic heart disease. Infection and Immunity, 73(4), 2496-2503. https://doi.org/10.1128/IAI.73.4.2496-2503.2005

Role of endothelin 1 in the pathogenesis of chronic chagasic heart disease. / Tanowitz, Herbert B.; Huang, Huan; Jelicks, Linda A.; Chandra, Madhulika; Loredo, Maria L.; Weiss, Louis M.; Factor, Stephen M.; Shtutin, Vitaliy; Mukherjee, Shankar; Kitsis, Richard N.; Christ, George J.; Wittner, Murray; Shirani, Jamshid; Kisanuki, Yaz Y.; Yanagisawa, Masashi.

In: Infection and Immunity, Vol. 73, No. 4, 04.2005, p. 2496-2503.

Research output: Contribution to journalArticle

Tanowitz, HB, Huang, H, Jelicks, LA, Chandra, M, Loredo, ML, Weiss, LM, Factor, SM, Shtutin, V, Mukherjee, S, Kitsis, RN, Christ, GJ, Wittner, M, Shirani, J, Kisanuki, YY & Yanagisawa, M 2005, 'Role of endothelin 1 in the pathogenesis of chronic chagasic heart disease', Infection and Immunity, vol. 73, no. 4, pp. 2496-2503. https://doi.org/10.1128/IAI.73.4.2496-2503.2005
Tanowitz HB, Huang H, Jelicks LA, Chandra M, Loredo ML, Weiss LM et al. Role of endothelin 1 in the pathogenesis of chronic chagasic heart disease. Infection and Immunity. 2005 Apr;73(4):2496-2503. https://doi.org/10.1128/IAI.73.4.2496-2503.2005
Tanowitz, Herbert B. ; Huang, Huan ; Jelicks, Linda A. ; Chandra, Madhulika ; Loredo, Maria L. ; Weiss, Louis M. ; Factor, Stephen M. ; Shtutin, Vitaliy ; Mukherjee, Shankar ; Kitsis, Richard N. ; Christ, George J. ; Wittner, Murray ; Shirani, Jamshid ; Kisanuki, Yaz Y. ; Yanagisawa, Masashi. / Role of endothelin 1 in the pathogenesis of chronic chagasic heart disease. In: Infection and Immunity. 2005 ; Vol. 73, No. 4. pp. 2496-2503.
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