Role of NO Synthase in the Development of Trypanosoma cruzi-Induced Cardiomyopathy in Mice

Department of Physiology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
The American journal of tropical medicine and hygiene (Impact Factor: 2.7). 06/2009; 80(5):782-7.
Source: PubMed


Trypanosoma cruzi infection results in an increase in myocardial NO and intense inflammation. NO modulates the T. cruzi-induced myocardial inflammatory reaction. NO synthase (NOS)1-, NOS2-, and NOS3-null mice were infected with T. cruzi (Brazil strain). Infected NOS1-null mice had increased parasitemia, mortality, and left ventricular inner diameter (LVID). Chronically infected NOS1- and NOS2-null and wild-type mice (WT) exhibited increased right ventricular internal diameter (RVID), although the fold increase in the NOS2-null mice was smaller. Infected NOS3-null mice exhibited a significant reduction both in LVID and RVID. Reverse transcriptase-polymerase chain reaction showed expression of NOS2 and NOS3 in hearts of infected NOS1-null and WT mice, whereas infected NOS2-null hearts showed little change in expression of other NOS isoforms. Infected NOS3-null hearts showed an increase only in NOS1 expression. These results may indicate different roles for NOS isoforms in T. cruzi-induced cardiomyopathy.

Full-text preview

Available from:
  • Source
    • "Both eNOS and nNOS act as constitutively expressed proteins, and their expression is not limited to endothelial cells or neurons.9 In fact, NO is produced from both nNOS and eNOS during infection and autoimmunity.10-12 Cell types that contain eNOS and nNOS generate low fluxes of NO for short periods of time. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Nitric oxide (NO) is a short-lived, diatomic, lipophilic gas that plays an integral role in defending against pathogens. Among its many functions are involvement in immune cell signaling and in the biochemical reactions by which immune cells defend against bacteria, fungi, viruses and parasites. NO signaling directs a broad spectrum of processes, including the differentiation, proliferation, and apoptosis of immune cells. When secreted by activated immune cells, NO diffuses across cellular membranes and exacts nitrosative and oxidative damage on invading pathogens. These observations led to the development of NO delivery systems that can harness the antimicrobial properties of this evanescent gas. The innate microbicidal properties of NO, as well as the antimicrobial activity of the various NO delivery systems, are reviewed.
    Full-text · Article · May 2012 · Virulence
  • Source
    • "qPCR analysis demonstrated a significant upregulation at day 15 postinfection of the mRNA levels of NOS-2 (200-fold increase) and superoxide dismutase (Sod1: 7.5-fold increase) in hearts obtained from infected mice compared to uninfected mice. T. cruzi infection has been previously reported to upregulate NOS2, NOS3, and NOS1 levels (Durand et al. 2009). Mice treated with curcumin demonstrated a significant decrease in the mRNA levels of enzymes involved in oxidative signaling such as catalase, peroxidase, SOD, NOS2, and NOS1 in heart tissue compared to untreated infected mice heart as determined by qPCR analysis at day 20 p.i. (Table 2). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Trypanosoma cruzi, the etiologic agent of Chagas disease, causes an acute myocarditis and chronic cardiomyopathy. The current therapeutic agents for this disease are not always effective and often have severe side effects. Curcumin, a plant polyphenol, has demonstrated a wide range of potential therapeutic effects. In this study, we examined the effect of curcumin on T. cruzi infection in vitro and in vivo. Curcumin pretreatment of fibroblasts inhibited parasite invasion. Treatment reduced the expression of the low density lipoprotein receptor, which is involved in T. cruzi host cell invasion. Curcumin treatment of T. cruzi-infected CD1 mice reduced parasitemia and decreased the parasitism of infected heart tissue. This was associated with a significant reduction in macrophage infiltration and inflammation in both the heart and liver; moreover, curcumin-treated infected mice displayed a 100% survival rate in contrast to the 60% survival rate commonly observed in untreated infected mice. These data are consistent with curcumin modulating infection-induced changes in signaling pathways involved in inflammation, oxidative stress, and apoptosis. These data suggest that curcumin and its derivatives could be a suitable drug for the amelioration of chagasic heart disease.
    Preview · Article · Jan 2012 · Parasitology Research
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Nitric oxide (NO) is a free radical synthesized from L-arginine by three different NO-synthases (NOS). NO exhibits multiple and complex biological functions and many of its effects can be mostly attributed to its strong oxidant capacity, which provides it a high affinity to metals, mainly metal with low spin configuration. Molecular targets of NO are diverse and include both low molecular weight species (e.g. thiols) and macromolecules that can be either activated or inhibited as a consequence of reacting with NO. Thus, NO is an important mediator of immune homeostasis and host defence, and changes in its generation or actions can contribute to pathologic states. The knowledge of novel effects of NO has been not only an important addition to our understanding of immunology but also a foundation for the development of new approaches for the management and treatment of various diseases, including Chagas' disease. Herein, the multiple mechanisms by which NO can directly or indirectly affect the generation of an immune response against T. cruzi infection are discussed.
    Full-text · Article ·
Show more