Myocardial expression of endothelin-1 in murine Trypanosoma cruzi infection

Cardiovasc Pathol. 2000 Sep-Oct;9(5):257-65. doi: 10.1016/s1054-8807(00)00045-4.

Abstract

Chagas' disease, caused by Trypanosoma cruzi, is an important cause of myocarditis and chronic cardiomyopathy and is accompanied by microvascular spasm and myocardial ischemia. We reported previously that infection of cultured endothelial cells with T. cruzi increased the synthesis of biologically active endothlein-1 (ET-1). In the present study, we examined the role of ET-1 in the cardiovascular system of CD1 mice infected with the Brazil strain of T. cruzi and C57BL/6 mice infected with the Tulahuen strain during acute infection. In the myocardium of infected mice myonecrosis and multiple pseudocysts were observed. There was also an intense vasculitis of the aorta, coronary artery, smaller myocardial vessels and the endocardial endothelium. Immunohistochemistry studies employing anti-ET-1 antibody revealed increased expression of ET-1 that was most intense in the endocardial and vascular endothelium. Elevated levels of mRNA for preproET-1, endothelin converting enzyme and ET-1 were observed in the same myocardial samples. Plasma ET-1 levels were significantly elevated in infected CD1 mice 10-15 days post infection. These observations suggest that increased levels of ET-1 are a consequence of the initial invasion of the cardiovascular system and provide a mechanism for infection-associated myocardial dysfunction.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aspartic Acid Endopeptidases / genetics
  • Aspartic Acid Endopeptidases / metabolism
  • Biomarkers
  • Chagas Cardiomyopathy / metabolism*
  • Chagas Cardiomyopathy / parasitology
  • Coronary Vessels / parasitology
  • Coronary Vessels / pathology
  • DNA Primers / chemistry
  • Endothelin-1 / genetics
  • Endothelin-1 / metabolism*
  • Endothelin-Converting Enzymes
  • Endothelins / genetics
  • Endothelins / metabolism
  • Endothelium, Vascular / parasitology
  • Endothelium, Vascular / pathology
  • Male
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Myocardial Ischemia / metabolism
  • Myocardial Ischemia / parasitology
  • Myocarditis / metabolism
  • Myocarditis / parasitology
  • Myocardium / metabolism*
  • Protein Precursors / genetics
  • Protein Precursors / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trypanosoma cruzi / isolation & purification*

Substances

  • Biomarkers
  • DNA Primers
  • Endothelin-1
  • Endothelins
  • Protein Precursors
  • RNA, Messenger
  • Aspartic Acid Endopeptidases
  • Metalloendopeptidases
  • Endothelin-Converting Enzymes