scholarly journals Cardiac Chagas Disease: MMPs, TIMPs, Galectins, and TGF-β as Tissue Remodelling Players

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Arthur Wilson Florencio da Costa ◽  
Jose Rodrigues do Carmo Neto ◽  
Yarlla Loyane Lira Braga ◽  
Beatriz Aquino Silva ◽  
Amanda Borges Lamounier ◽  
...  
Keyword(s):  
Heart Disease ◽  
Chagas Disease ◽  
Cardiac Tissue ◽  
Tissue Remodeling ◽  
Tissue Remodelling ◽  
Tissue Inhibitors ◽  
Inflammatory Microenvironment ◽  
Target Organs ◽  
Chagas Heart Disease ◽  
Host Parasite

A century after the discovery of Chagas disease, studies are still needed to establish the complex pathophysiology of this disease. However, it is known that several proteins and molecules are related to the establishment of this disease, its evolution, and the appearance of its different clinical forms. Metalloproteinases and their tissue inhibitors, galectins, and TGF-β are involved in the process of infection and consequently the development of myocarditis, tissue remodeling, and fibrosis upon infection with Trypanosoma cruzi. Thus, considering that the heart is one of the main target organs in Chagas disease, knowledge regarding the mechanisms of action of these molecules is essential to understand how they interact and trigger local and systemic reactions and, consequently, determine whether they contribute to the development of Chagas’ heart disease. In this sense, it is believed that the inflammatory microenvironment caused by the infection alters the expression of these proteins favoring progression of the host-parasite cycle and thereby stimulating cardiac tissue remodeling mechanisms and fibrosis. The aim of this review was to gather information on metalloproteinases and their tissue inhibitors, galectins, and TGF-β and discuss how these molecules and their different interrelationships contribute to the development of Chagas’ heart disease.

scholarly journals Ethiological treatment of acute and chronic Chagas' heart disease

1995 ◽  
Vol 113 (2) ◽  
pp. 867-872 ◽  
Author(s):  
Abílio Augusto Fragata Filho ◽  
Marco Aurélio Dias da Silva ◽  
Elias Boainain
Keyword(s):  
Heart Disease ◽  
Chagas Disease ◽  
Acute Phase ◽  
Randomized Trials ◽  
Research Protocol ◽  
Infection Route ◽  
End Of Treatment ◽  
Toxic Agents ◽  
Chagas Heart Disease

The uncertaintties in the ethiological treatment of Chagas' Disease are consequence of the lack of entire knowledge of its pathogeny and the no existence of a healing criterium. There is a consensus that antiparasite drugs should be used in the acute phase of the infection, regardless of the infection route, in new crisis, in patients under immunossuppression and in organs transplantation. There is still controversy regarding subacute, chronic or indetermined phase or cases with mild cardiac/digestive forms, not included in the situations listed above neither in a research protocol. The treatment includes oral benzonidazol 5 mg/kg/day, bid or tid for 60 days. In 71 patients monitored in this fashion, the authors have found 60% of negative xenodiagnostic at the end of treatment. It is still necessary, however, to continue to investigate and accomplishing more randomized trials to confirm the efficacy of such method, and also to try to obtain effective and less toxic agents. It is also fundamental to standardize a more reliable healing criterium.

scholarly journals Tumor Necrosis Factor Is a Therapeutic Target for Immunological Unbalance and Cardiac Abnormalities in Chronic Experimental Chagas’ Heart Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Isabela Resende Pereira ◽  
Glaucia Vilar-Pereira ◽  
Andrea Alice Silva ◽  
Otacilio Cruz Moreira ◽  
Constança Britto ◽  
...  
Keyword(s):  
T Cells ◽  
Heart Disease ◽  
Tumor Necrosis ◽  
Cardiac Tissue ◽  
Cardiac Abnormalities ◽  
Chagas Heart Disease ◽  
Chagasic Cardiomyopathy ◽  
Inflammatory Profile ◽  
Fibronectin Deposition ◽  
Necrosis Factor

Background. Chagas disease (CD) is characterized by parasite persistence and immunological unbalance favoring systemic inflammatory profile. Chronic chagasic cardiomyopathy, the main manifestation of CD, occurs in a TNF-enriched milieu and frequently progresses to heart failure.Aim of the Study. To challenge the hypothesis that TNF plays a key role inTrypanosoma cruzi-induced immune deregulation and cardiac abnormalities, we tested the effect of the anti-TNF antibody Infliximab in chronicallyT. cruzi-infected C57BL/6 mice, a model with immunological, electrical, and histopathological abnormalities resembling Chagas’ heart disease.Results. Infliximab therapy did not reactivate parasite but reshaped the immune response as reduced TNF mRNA expression in the cardiac tissue and plasma TNF and IFNγlevels; diminished the frequency of IL-17A+but increased IL-10+CD4+T-cells; reduced TNF+but augmented IL-10+Ly6C+and F4/80+cells. Further, anti-TNF therapy decreased cytotoxic activity but preserved IFNγ-producing VNHRFTLV-specific CD8+T-cells in spleen and reduced the number of perforin+cells infiltrating the myocardium. Importantly, Infliximab reduced the frequency of mice afflicted by arrhythmias and second degree atrioventricular blocks and decreased fibronectin deposition in the cardiac tissue.Conclusions. Our data support that TNF is a crucial player in the pathogenesis of Chagas’ heart disease fueling immunological unbalance which contributes to cardiac abnormalities.

scholarly journals A doença de chagas e a cardiopatia chagásica crônica: uma revisão de literatura / Chagas disease and chronic chagas heart disease: literature review

2021 ◽  
Vol 7 (12) ◽  
pp. 112598-112615
Author(s):  
Camila Maria Braga Tameirão ◽  
Luiza Junqueira de Miranda ◽  
Maria Eduarda Ferreira Gomes ◽  
Maria Gabriela Elias D’Assumpção ◽  
Milton Henriques Guimarães Junior
Keyword(s):  
Heart Disease ◽  
Literature Review ◽  
Chagas Disease ◽  
Chagas Heart Disease

scholarly journals Heart transplants for patients with Chagas' heart disease

1995 ◽  
Vol 113 (2) ◽  
pp. 873-879 ◽  
Author(s):  
Edimar Alcides Bocchi
Keyword(s):  
Heart Disease ◽  
Chagas Disease ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Heart Transplants ◽  
Ventricular Ejection Fraction ◽  
Chagas Heart Disease ◽  
The Mean ◽  
Cruzi Infection

The role of heart transplants for treating Chagas' heart disease is not quite clear. Immunosuppression could lead to resurgence of T. cruzi infection with acute or chronic damage to the allograft. There are few publications regarding this issue. Thus we reported the follow-up of 18-patients with Chagas' heart disease submitted to orthotopic heart transplants from 1985 to 1993 at The Heart Institute. The patients were in functional class IV or III, or II, with sustained ventricular tachycardia episodes. The mean left ventricular ejection fraction was 25 ± 9% and the mean right ventricular ejection was 22 ± 6% (MUGA). Immunosuppression was based on cyclosporin, azathioprine and corticosteroids. For specific post-transplant monitoring of T. cruzi infection, blood tests were performed (examination of blood or leukocyte concentrate, Giemsa-stained blood smears, blood culture, xenodiagnosis, mouse inoculation) and tissue biopsy (skin or myocardium). In addition, complement fixation hemagglutination and immunofluorescence assays were performed. T. cruzi parasitemias were detected in 18 circumstances in 13 patients. Resurgence of Chagas' disease was diagnosed in 11 circumstances in 5 patients. Fever, subcutaneous nodules and myocarditis predominated in these episodes. All episodes of parasitemia and Chagas' disease resurgence were successfully treated with benzonidazole. All surviving patients had normal cardiac function despite left ventricular function worsening during some myocarditis episodes. Neoplasias were important findings and 3 patients developed lymphoproliferative disease, 2 developed Karposi's sarcoma and 1 patient developed skin cancer. The survival rates at 4 and 12 months were 83% and 49% respectively. The survival of patients who underwent heart transplants from August 1991 to April 1993 was 100% at 4 months and 75% at 12 months. Heart transplants for Chagas' heart disease may be associated with episodes of parasitemia and a reoccurrence of episodes of Chaga's disease. The survival of heart transplanted patients has improved when associated with lower doses of cyclosporins and thus, fewer resurgences of the disease.

scholarly journals Effects of an exercise program on blood pressure in patients with treated hypertension and chronic Chagas' heart disease

2012 ◽  
Vol 45 (6) ◽  
pp. 727-731 ◽  
Author(s):  
Claudia Rosa de Oliveira ◽  
Andréa Silvestre de Sousa ◽  
Bráulio Santos ◽  
Paloma Hargreaves Fialho ◽  
Carla Cristiane Soares dos Santos ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Disease ◽  
Chagas Disease ◽  
Blood Pressure Monitoring ◽  
Exercise Program ◽  
Study Results ◽  
Before And After ◽  
Chagas Heart Disease ◽  
Blood Pressures ◽  
Chronic Chagas Disease

INTRODUCTION: Previous studies describe an imbalance of the autonomic nervous system in Chagas' disease causing increased sympathetic activity, which could influence the genesis of hypertension. However, patients undergoing regular physical exercise could counteract this condition, considering that exercise causes physiological responses through autonomic and hemodynamic changes that positively affect the cardiovascular system. This study aimed to evaluate the effects of an exercise program on blood pressure in hypertensive patients with chronic Chagas' heart disease. METHODS: We recruited 17 patients to a 24-week regular exercise program and used ambulatory blood pressure monitoring before and after training. We determined the differences in the systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) from the beginning to the end of the study. RESULTS: The blood pressures were evaluated in general and during periods of wakefulness and sleep, respectively: SBP (p = 0.34; 0.23; 0.85), DBP (p = 0.46; 0.44; 0.94) and MBP (p = 0.41; 0.30; 0.97). CONCLUSIONS: There was no statistically significant change in blood pressure after the 24-week exercise program; however, we concluded that physical training is safe for patients with chronic Chagas' disease, with no incidence of increase in blood pressure.

scholarly journals Effects of an exercise program on the functional capacity of patients with chronic Chagas' heart disease, evaluated by cardiopulmonary testing

2012 ◽  
Vol 45 (2) ◽  
pp. 220-224 ◽  
Author(s):  
Paloma Hargreaves Fialho ◽  
Bernardo Rangel Tura ◽  
Andréa Silvestre de Sousa ◽  
Claudia Rosa de Oliveira ◽  
Carla Cristiane Santos Soares ◽  
...  
Keyword(s):  
Heart Disease ◽  
Chagas Disease ◽  
Functional Capacity ◽  
Severe Heart Failure ◽  
Exercise Program ◽  
Public Health Problem ◽  
Cardiopulmonary Exercise Test ◽  
Regular Exercise ◽  
Aerobic Activity ◽  
Chagas Heart Disease

INTRODUCTION: Despite all efforts to restrict its transmission, Chagas' disease remains a severe public health problem in Latin America, affecting 8-12 million individuals. Chronic Chagas' heart disease, the chief factor in the high mortality rate associated with the illness, affects more than half a million Brazilians. Its evolution may result in severe heart failure associated with loss of functional capacity and quality of life, with important social and medical/labor consequences. Many studies have shown the beneficial effect of regular exercise on cardiac patients, but few of them have focused on chronic Chagas' heart disease. METHODS: This study evaluated the effects of an exercise program on the functional capacity of patients with chronic Chagas' disease who were treated in outpatient clinics at the Evandro Chagas Institute of Clinical Research and the National Institute of Cardiology, Rio de Janeiro, Brazil. The exercises were performed 3 times a week for 1 h (30 min of aerobic activity and 30 min of resistance exercises and extension) over 6 months in 2010. Functional capacity was evaluated by comparing the direct measurement of the O2 uptake volume (VO2) obtained by a cardiopulmonary exercise test before and after the program (p < 0.05). RESULTS: Eighteen patients (13 females) were followed, with minimum and maximum ages of 30 and 72 years, respectively. We observed an average increase of VO2peak > 10% (p = 0.01949). CONCLUSIONS: The results suggest a statistically significant improvement in functional capacity with regular exercise of the right intensity.

scholarly journals Ventricular function in Chagas' heart disease

1995 ◽  
Vol 113 (2) ◽  
pp. 814-820 ◽  
Author(s):  
Benedito Carlos Maciel ◽  
Oswaldo César de Almeida Filho ◽  
André Schmidt ◽  
José Antonio Marin-Neto
Keyword(s):  
Heart Rate ◽  
Heart Disease ◽  
Ventricular Function ◽  
Chagas Disease ◽  
Loading Conditions ◽  
Noninvasive Methods ◽  
Ventricular Performance ◽  
Chagas Heart Disease

Invasive and noninvasive methods used to evaluate ventricular function in Chagas's disease are reviewed. The traditional indices of overall ventricular performance reflect interaction of preload, contractility, afterload and heart rate. Therefore, they are unable to distinguish changes in contractility from modifications of loading conditions. The role of ventricular function as a predictor of mortality in chronic Chagas' heart disease is discussed. Ventricular function abnormalities in patients with indeterminate and digestive forms of Chagas' disease are especially emphasized. Finally, the evidence of early impairment of diastolic performance in patients with Chagas' disease is presented.

scholarly journals Pathology and Pathogenesis of Chagas Heart Disease

2019 ◽  
Vol 14 (1) ◽  
pp. 421-447 ◽  
Author(s):  
Kevin M. Bonney ◽  
Daniel J. Luthringer ◽  
Stacey A. Kim ◽  
Nisha J. Garg ◽  
David M. Engman
Keyword(s):  
Heart Disease ◽  
Protozoan Parasite ◽  
The United States ◽  
Western Hemisphere ◽  
Susceptibility To Infection ◽  
Chagas Heart Disease ◽  
Ultimate Outcome ◽  
Host Parasite ◽  
Adverse Sequela ◽  
Cruzi Infection

Chagas heart disease is an inflammatory cardiomyopathy that develops in approximately one-third of people infected with the protozoan parasite Trypanosoma cruzi. One way T. cruzi is transmitted to people is through contact with infected kissing bugs, which are found in much of the Western Hemisphere, including in vast areas of the United States. The epidemiology of T. cruzi and Chagas heart disease and the varied mechanisms leading to myocyte destruction, mononuclear cell infiltration, fibrosis, and edema in the heart have been extensively studied by hundreds of scientists for more than 100 years. Despite this wealth of knowledge, it is still impossible to predict what will happen in an individual infected with T. cruzi because of the tremendous variability in clonal parasite virulence and human susceptibility to infection and the lack of definitive molecular predictors of outcome from either side of the host–parasite equation. Further, while several distinct mechanisms of pathogenesis have been studied in isolation, it is certain that multiple coincident mechanisms combine to determine the ultimate outcome. For these reasons, Chagas disease is best considered a collection of related but distinct illnesses. This review highlights the pathology and pathogenesis of the most common adverse sequela of T. cruzi infection—Chagas heart disease—and concludes with a discussion of key unanswered questions and a view to the future.

scholarly journals Studies of the coronary circulation in Chagas' heart disease

1995 ◽  
Vol 113 (2) ◽  
pp. 826-834 ◽  
Author(s):  
José Antonio Marin-Neto ◽  
Marcus V. Simões ◽  
Elias M. Ayres-Neto ◽  
J. Luiz Attab-Santos ◽  
L. Gallo Jr. ◽  
...  
Keyword(s):  
Heart Disease ◽  
Chagas Disease ◽  
Coronary Arteries ◽  
Coronary Circulation ◽  
Myocardial Damage ◽  
Experimental Models ◽  
Chronic Patients ◽  
Chagas Heart Disease ◽  
Artery Disease ◽  
Myocardial Lesions

Pathogenesis of chronic Chagas' heart disease may include various disturbances in the coronary circulation, that could be responsible for the myocardial lesions seen in human hearts and in experimental models of the disease. In this paper we critically reviewed the anatomical and functional abnormalities described in chronic chagasic patients, pertaining to the so-called vascular pathogenetic theory of Chagas' disease. The epicardial coronary arteries are usually free of significant obstructive disease in nonselected groups of chagasic patients examined at autopsy or by coronary angiography. However, chagasic patients who were studied after an episode of acute myocardial infarction, show the same patterns of atherosclerotic coronary artery disease seen in the general nonchagasic population. Studies of chagasic patients with angiographically normal coronary arteries, by several scintigraphy methods, revealed myocardial perfusion abnormalities which may be caused by the microcirculatory derangements described in animals experimentally infected with the T. cruzi. Since hypoperfusion has been detected in regions with normal or mildly impaired wall motion, it is likely that the microvascular disturbances precede and may be a causative mechanism for the subsequent myocardial damage. We speculate that hibernating ventricular areas may occur in chagasic patients, on the basis of the evidence gathered from these studies. Recent investigations of chronic patients with Chagas' disease and chest pain showed attenuation of the vasomotor responses to physiological and pharmacological stimuli, in the epicardial coronary arteries.

scholarly journals Diversity of Trypanosoma cruzi stocks and clones derived from Chagas disease patients: I-Behavioral characterization in vitro

1997 ◽  
Vol 30 (3) ◽  
pp. 187-192 ◽  
Author(s):  
L. Lauria-Pires ◽  
J.M. Santana ◽  
F.S. Tavares ◽  
A.R.L. Teixeira
Keyword(s):  
Heart Disease ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Disease Patient ◽  
Behavioral Diversity ◽  
Parental Stock ◽  
Chagas Heart Disease ◽  
Clonal Lines ◽  
Behavioral Characterization

In this study, we isolated Trypanosoma cruzi from chronic Chagas heart disease and from megaesophagus patients. The parasite stock hSLU239 (heart disease) yielded clones h1 and h2, whereas stock mSLU142 (megaesophagus) yielded clones m1, m2, m3 and m4. The parasite growth kinetics, doubling time and differentiation in axenic liquid medium showed broad behavioral diversity. It was shown that a particular pattern of behavior for a parental stock could not necessarily be assigned for subsequent clones. This study indicates that i) each Chagas disease patient is infected with several T. cruzi populations; ii) clonal lines derived from patient samples may have different biological characteristics from the original isolate; and that iii) additional behavioral and/or molecular markers are required for further characterization of Trypanosoma cruzi stocks and clones derived from Chagas disease patients in order to identify correlations with pathology.

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