Role of cardiac myocyte-derived endothelin-1 in chagasic cardiomyopathy: Molecular genetic evidence

Huan Huang, Masashi Yanagisawa, Yaz Y. Kisanuki, Linda A. Jelicks, Madhulika Chandra, Stephen M. Factor, Murray Wittner, Louis M. Weiss, Richard G. Pestell, Vitaliy Shtutin, Jamshid Shirani, Herbert B. Tanowitz

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Trypanosoma cruzi is the aetiological agent of Chagas' disease, an important cause of chronic cardiomyopathy. We previously demonstrated a role for endothelin-1 (ET-1) in the pathogenesis of chagasic heart disease. In order to explore further the significance of ET-1 in chagasic heart disease, we infected ET-1 (flox/flox); α-MHC-Cre(+) (ET-IKO) mice, in which the ET-1 gene has been deleted from cardiac myocytes, with 104 T. cruzi (Brazil strain) trypomastigotes. As controls, we used ET-1 (flox/flox);Cre(-) (FLOX) and C57BL/6 × 129sv (WT) mice. All mice survived and were evaluated 150-160 days post-infection. Cardiac magnetic resonance imaging revealed a significant increase in right ventricular internal diameter in all infected animals except ET-IKO mice (control WT, 1.6±0.10 mm; infected WT, 2.8±0.15 mm; control FLOX, 2.04±0.02 mm; infected FLOX, 2.76±0.28 mm). There was no significant difference in right ventricular internal diameter between infected and uninfected ET-IKO mice (control ET-IKO, 1.83±0.11 mm; infected ET-IKO, 2.14±0.20 mm). In another series of experiments, transthoracic echocardiography was performed on uninfected as well as infected ET-IKO mice, and uninfected and infected FLOX mice. Both infected groups had an increased left ventricular end-diastolic diameter and reduced fractional shortening. In addition, relative wall thickness was also decreased in infected animals. However, the magnitude of these changes was less in infected ET-IKO mice. These data provide further support for a role for ET-1 in the pathogenesis of chronic chagasic heart disease, and indicate that cardiac myocytes are an important source of ET-1 in this disease.

Original languageEnglish (US)
Pages (from-to)263S-266S
JournalClinical science
Volume103
Issue numberSUPPL. 48
StatePublished - Aug 1 2002

Keywords

  • Chagas' disease
  • Endothetin-1
  • Trypanosoma cruzi

ASJC Scopus subject areas

  • Medicine(all)

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    Huang, H., Yanagisawa, M., Kisanuki, Y. Y., Jelicks, L. A., Chandra, M., Factor, S. M., Wittner, M., Weiss, L. M., Pestell, R. G., Shtutin, V., Shirani, J., & Tanowitz, H. B. (2002). Role of cardiac myocyte-derived endothelin-1 in chagasic cardiomyopathy: Molecular genetic evidence. Clinical science, 103(SUPPL. 48), 263S-266S.