ArticlesMyocardial Expression of Endothelin-1 in Murine Trypanosoma cruzi Infection
Section snippets
Infection of Mice
Eight- to ten-week-old male CD1 mice (Jackson Laboratories, Bar Harbor, ME) were infected with 104 trypomastigotes of the Brazil strain of T. cruzi. Eight-week old C57BL/6 mice (Jackson Laboratories, Bar Harbor, ME) were infected with 104 trypomastigotes of the Tulahuen strain. Hearts were obtained at various time-points post-infection, for histology, immunohistochemistry, and total RNA isolation.
Histology
Hearts were fixed in 10% buffered formalin and stained with hematoxylin and eosin. The slides were
Infection of Mice
Infected CD1 mice had achieved a parasitemia of 106 to 107 trypomastigotes/ml blood by day 30–35 post infection, at which time the mortality rate was 30–50% (21). Infected C57BL/6 mice had 100% mortality by day 20–25 post infection, when the parasitemia was 106–107/ml.
Histology
During acute infection in both mouse models there were intense myonecrosis and multiple areas of pseudocyst formation Figure 1, Figure 2. Necrosis and vasculitis were more severe in the Tulahuen-infected C57BL/6 mice compared with
Discussion
The role of ET-1 in murine T. cruzi infection was investigated in CD1 mice infected with the Brazil strain and the C57BL/6 mouse infected with the Tulahuen strain. In the CD1 model there is a significant mortality by 30–35 days post infection, with a moderately high parasitemia and acute myocarditis and vasculitis. The mice that survive acute infection eventually develop a chronic cardiomyopathy. However, in the C57BL/6 model there is a high parasitemia and 100% mortality by day 25 of
Acknowledgements
These studies were supported in part by grants R01AI-12770 (HBT), R01AI-41752 (MW), R01DK46379 (GJC), and R01CA-75503, and R01CA70896 (RGP) from the National Institutes of Health. This work was also supported by a New Investigator Award (HH) and a Grant in Aid (HBT) from the Heritage Branch of the American Heart Association. We wish to thank Vicki Braunstein for excellent technical assistance.
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2019, Pharmacology and TherapeuticsCitation Excerpt :Furthermore, ET-1 causes platelet aggregation, and plays a role in the increased expression of leukocyte adhesion molecules and their synthesis of inflammatory mediators, thus contributing to vascular dysfunction (Matsuo, Mihara, Ninomiya, & Fujimoto, 2001; Teder & Noble, 2000). ET-1 is produced at significantly higher rates during a variety of infections (Dai et al., 2012; Dietmann et al., 2008; Koedel, Gorriz, Lorenzl, & Pfister, 1997; Machado et al., 2006; Martins et al., 2016; Petkova et al., 2000; Petkova et al., 2001; Wanecek, Weitzberg, Rudehill, & Oldner, 2000). In fact, ET-1 has been shown to contribute to the pathogenesis and severity of bacterial, viral and parasitic disease processes including sepsis, meningitis, pneumonia, rickettsial infections, Chagas disease and cerebral malaria (Dai et al., 2012; Davi et al., 1995; Freeman et al., 2016; Goto et al., 2012; Koedel et al., 1997; Martins et al., 2016; Petkova et al., 2000; Petkova et al., 2001; Samransamruajkit et al., 2002; Schuetz et al., 2008; Tschaikowsky, Sagner, Lehnert, Kaul, & Ritter, 2000; Wanecek et al., 2000; Wenisch et al., 1996).
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2017, Advances in ParasitologyCitation Excerpt :ET-1 is a vasoactive peptide synthesized by many cell types including cardiac myocytes and cardiac fibroblasts associated with vasospasm, vascular damage, cardiovascular remodelling and inflammation (Kedzierski and Yanagisawa, 2001). Mice infected with T. cruzi exhibit increased levels of ET-1 and endothelin-converting enzyme (ECE), the enzyme responsible for the conversion of the precursor to ET-1, in plasma, in the vasculature and in T. cruzi-infected myocardial cells (Huang et al., 2000; Petkova et al., 2000). Interestingly, phosphoramidon, an inhibitor of ECE, ameliorated the pathology and reduced the extent of cardiac remodelling in these animals (Jelicks et al., 2002).
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