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Studies of Membrane Fluidity and Heart Contractile Force In Trypanosoma Cruzi Infected Mice
Memórias do Instituto …, 2004
In Chagas disease serious cardiac dysfunction can appear. We specifically studied the cardiac function by evaluating: ventricle contractile force and norepinephrine response, affinity and density of β-adrenergic receptors, dynamic properties of myocardial membranes, and electrocardiography. Albino swiss mice (n = 250) were infected with 55 trypomastigotes, Tulahuen strain and studied at 35, 75, and 180 days post-infection, that correspond to the acute, indeterminate, and chronic phase respectively. Cardiac β-adrenergic receptors' affinity, myocardial contractility, and norepinephrine response progressively decreased from the acute to the chronic phase of the disease (p < 0.01). The density (expressed as fmol/mg.prot) of the receptors was similar to non-infected mice (71.96 ± 0.36) in both the acute (78.24 ± 1.67) and indeterminate phases (77.28 ± 0.91), but lower in the chronic disease (53.32 ± 0.71). Electrocardiographic abnormalities began in the acute phase and were found in 65% of the infected-mice during the indeterminate and chronic phases. Membrane contents of triglycerides, cholesterol, and anisotropy were similar in all groups. A quadratic correlation between the affinity to β-adrenergic receptors and cardiac contractile force was obtained. In conclusion the changes in cardiac β-adrenergic receptors suggests a correlation between the modified β-adrenergic receptors affinity and the cardiac contractile force.
The FASEB Journal, 1998
Antibodies of chronic chagasic patients have been shown to interfere with electric and mechanical activities of cardiac embryonic myocytes in culture and with whole mammalian hearts. A mechanism proposed for this effect involves interaction of the antibodies with G-protein-linked membrane receptors, thus leading to activation of beta adrenergic and muscarinic receptors; more specifically, IgG of chagasic patients would interact with the negatively charged regions of the second extracellular loop of these receptors. We performed competition experiments to test this hypothesis. We evaluated the effect of sera/IgG from patients previously known to depress electrogenesis and/or atrioventricular conduction in isolated rabbit hearts after incubation with live and lysed parasites, the peptide corresponding to the second extracellular loop (O2) of the M2 receptor, and different peptides derived from two ribosomal proteins of T. cruzi: P0 and P2b. Our results indicate that 1) the antigenic factor inducing the functionally active IgGs in the chagasic patients is probably an intracellular T. cruzi antigen; 2) IgG/serum is interacting with the O2 region of the M2 receptor in the rabbit heart; and 3) the negative charges present in the ribosomal proteins of T. cruzi are important in mediating the interaction between the patients' serum/IgG and the receptor.
Immunopathological Mechanisms Underlying Cardiac Damage in Chagas Disease
Pathogens
In Chagas disease, the mechanisms involved in cardiac damage are an active field of study. The factors underlying the evolution of lesions following infection by Trypanosoma cruzi and, in some cases, the persistence of its antigens and the host response, with the ensuing development of clinically observable cardiac damage, are analyzed in this review.
Altered Cardiomyocyte Function and Trypanosoma cruzi Persistence in Chagas Disease
The American journal of tropical medicine and hygiene, 2016
Chagas disease, caused by the triatominae Trypanosoma cruzi, is one of the leading causes of heart malfunctioning in Latin America. The cardiac phenotype is observed in 20-30% of infected people 10-40 years after their primary infection. The cardiac complications during Chagas disease range from cardiac arrhythmias to heart failure, with important involvement of the right ventricle. Interestingly, no studies have evaluated the electrical properties of right ventricle myocytes during Chagas disease and correlated them to parasite persistence. Taking advantage of a murine model of Chagas disease, we studied the histological and electrical properties of right ventricle in acute (30 days postinfection [dpi]) and chronic phases (90 dpi) of infected mice with the Colombian strain of T. cruzi and their correlation to parasite persistence. We observed an increase in collagen deposition and inflammatory infiltrate at both 30 and 90 dpi. Furthermore, using reverse transcriptase polymerase cha...
Antibodies of chronic chagasic patients have been shown to interfere with electric and mechanical activities of cardiac embryonic myocytes in culture and with whole mammalian hearts. A mechanism proposed for this effect involves interaction of the antibodies with G-protein-linked membrane receptors, thus leading to activation of beta adrenergic and muscarinic receptors; more specifically, IgG of chagasic patients would interact with the negatively charged regions of the second extracellular loop of these receptors. We performed competition experiments to test this hypothesis. We evaluated the effect of sera/IgG from patients previously known to depress electrogenesis and/or atrioventricular conduction in isolated rabbit hearts after incubation with live and lysed parasites, the peptide corresponding to the second extracellular loop (O2) of the M2 receptor, and different peptides derived from two ribosomal proteins of T. cruzi: P0 and P2b. Our results indicate that 1) the antigenic factor inducing the functionally active IgGs in the chagasic patients is probably an intracellular T. cruzi antigen; 2) IgG/serum is interacting with the O2 region of the M2 receptor in the rabbit heart; and 3) the negative charges present in the ribosomal proteins of T. cruzi are important in mediating the interaction between the patients' serum/IgG and the receptor.-Masuda, M. O., Levin, M., Farias de Oliveira, S., dos Santos Costa, P. C., Bergami, P. L., dos Santos Almeida, N. A., Pedrosa, R. C., Ferrari, I., Hoebeke, J., Campos de Carvalho, A. C. Functionally active cardiac antibodies in chronic Chagas' disease are specifically blocked by Trypanosoma cruzi antigens. FASEB J. 12, 1551-1558 (1998)
Parasitology, 2014
Antibodies (Ab) recognizing G-protein coupled receptors, such as β 1 and β 2 adrenergic (anti-β 1 -AR and anti-β 2 -AR, respectively) and muscarinic cholinergic receptors (anti-M 2 -CR) may contribute to cardiac damage, however their role in chronic chagasic cardiomyopathy is still controversial. We describe that Trypanosoma cruzi-infected C3H/He mice show increased P and QRS wave duration, and PR and QTc intervals, while the most significant ECG alterations in C57BL/6 are prolonged P wave and PR interval. Echocardiogram analyses show right ventricle dilation in infected animals of both mouse lineages. Analyses of heart rate variability (HRV) in chronically infected C3H/He mice show no alteration of the evaluated parameters, while C57BL/6 infected mice display significantly lower values of HRV components, suggesting autonomic dysfunction. The time-course analysis of anti-β 1 -AR, anti-β 2 -AR and anti-M 2 -CR Ab titres in C3H/He infected mice indicate that anti-β 1 -AR Ab are detected only in the chronic phase, while anti-β 2 -AR and anti-M 2 -CR are observed in the acute phase, diminish at 60 dpi and increase again in the chronic phase. Chronically infected C57BL/6 mice presented a significant increase in only anti-M 2 -CR Ab titres. Furthermore, anti-β 1 -AR, anti-β 2 -AR and anti-M 2 -CR, exhibit significantly higher prevalence in chronically T. cruzi-infected C3H/He mice when compared with C57BL/6. These observations suggest that T. cruzi infection leads to host-specific cardiac electric alterations.
Weekly electrocardiographic pattern in mice infected with two different Trypanosoma cruzi strains
International Journal of Cardiology, 2005
Background: Chagas' disease, which is caused by Trypanosoma cruzi, affects 20 million people. The electrocardiographic alterations are usually the first evidence of disease progression. In this work, we evaluated if two different T. cruzi strains presented electrocardiographic and heart histopathological alterations that could be characteristic and only achieved to the parasite strain. The moment when the electric alterations began was also studied. Methods: Albino mice (n=100) were inoculated with 50 (n=50) and 500 (n=50) trypomastigotes of T. cruzi, for Tulahuen strain and SGO-Z12 isolate, respectively. Electrocardiograms were obtained before infection and once a week from 7 to 147 days post infection (d.p.i). Dipolar and unipolar leads were analyzed. Hearts were removed by necropsy on 14, 90 and 147 d.p.i. Each heart was cut horizontally into 5-Am sections and they were stained with Hematoxilin-Eosine. Results: At 147 d.p.i., 30% of Tul-infected mice were found alive, while in the SGO-Z12 infected group, 75% were alive at the same moment. The Tul-infected group showed more intraventricular blockage alterations than the other groups from 49 to 70 d.p.i, (pb0.01). No structural cardiac alterations were detected in SGO-Z12-infected mice at 7 d.p.i., while the Tul-infected group showed mononuclear cell infiltrates. At 147 d.p.i., fiber disorganization and cell infiltration were observed in the SGO-Z12 and Tul-infected groups. Conclusions: We demonstrated that T. cruzi Tulahuen strain and SGO-Z12 isolate determined different electrocardiographic alterations which were characteristic for each stage of the experimental Chagas' disease. These results highlight the importance of the T. cruzi strain in the severity of the cardiopathy.
Pathogenesis of Chagas disease cardiomyopathy
World Journal of Clinical Infectious Diseases, 2012
Chagas disease, or American trypanosomiasis, is a parasitic infection caused by the flagellate protozoan Trypanosoma cruzi. Chagas disease is mainly affecting rural populations in Mexico and Central and South America. The World Health Organization estimates that 300 000 new cases of Chagas disease occur every year and approximately 20 000 deaths are attributable to Chagas. However, this organisation classified Chagas disease as a neglected tropical disease. The economic burden of this disease is significant. In many Latin American countries, the direct and indirect costs, including the cost of health care in dollars and loss of productivity, attributable to Chagas disease ranges from 40milliontoinexcessof40 million to in excess of 40milliontoinexcessof800 million per nation per annum. So, it remains a contemporary public health concern. In chronic phase, mortality is primarily due to the rhythm disturbances and congestive heart failure that result from the chronic inflammatory cardiomyopathy (CCC) due to the persistence presence of parasites in the heart tissue. Mechanisms underlying differential progression to CCC are still incompletely understood. In the last decades immunological proteomic genetic approaches lead to significant results which help to disperse the veil covering the knowledge of the pathogenic process. Here, we reported these significant progresses.
International Journal for Parasitology, 2008
The chronic indeterminate form of Trypanosoma cruzi infection could be the key to knowing which patients will develop chagasic myocardiopathy. Infected mice present a period in which cardiac functional and structural alterations are different from those described for acute or chronic phases. We studied some components of the cardiac b-adrenergic system in mouse hearts infected with T. cruzi Tulahuen strain or SGO-Z12 isolate during the chronic indeterminate phase of infection. We determined: (i) the primary messenger (epinephrine and norepinephrine) levels in plasma by reverse-phase-HPLC; (ii) the cardiac b-adrenergic receptors' (b-AR) density and affinity by binding with tritiated dihidroalprenolol and by immunofluorescence; (iii) the cardiac concentration of the second messenger (cAMP) (by ELISA) given its importance for the phosphorylation of the proteins involved in cardiac contraction; (iv) the cardiac contractility and functional studies of the b-ARs as a response to the ligand binding to the receptor; and (v) the left ventricular ejection fraction as a measure of in vivo cardiac function. Plasma catecholamines levels remained similar to those found in uninfected controls. The b-ARs' affinity decreased in both infected groups compared with the uninfected group (P < 0.05) while the receptors' density increased only in the SGO-Z12 group (P < 0.01). Cyclic AMP levels were higher in both infected groups (P < 0.01) relative to controls, and were higher in SGO-Z12-infected mice compared with those infected with the Tulahuen strain. However, the basal contractile force remained unchanged and the response to catecholamines only increased in the Tulahuen group (P < 0.05). The left ventricular ejection fraction, on the other hand, was diminished in SGO-Z12-infected mice. Heterogeneity between T. cruzi strains determine, in the chronic indeterminate form, alterations in the signaling pathways of the badrenergic system at different levels: (i) between catecholamines and the b 1 -receptors; (ii) between the receptors' activation and the adenylyl-cyclase activation; and/or (iii) between cAMP and the contractile response. Ó