Specific methylation marks in promoter regions are associated to the pathogenic process of Chronic Chagas disease Cardiomyopathy by modifying transcription factor binding patterns

Chagas disease, caused by Trypanosoma cruzi, is an endemic parasitical disease of Latin America, affecting 7 million people. Although most patients are asymptomatic, 30% develop complications, including Chronic Chagasic Cardiomyopathy (CCC), which ranges from moderate to severe stages depending on the cardiac ejection fraction. The pathogenic process remains poorly understood, although genetic and epigenetic factors have already been proposed. Based on bulk RNA-seq and EPIC methylation data, we investigated the genetic and epigenetic deregulations present in the moderate and severe stages of CCC. We identified 4 main biological processes associated with the pathology development, including immune response, ion transport, cardiac muscle processes and nervous system. An in-depth study of the transcription factors binding sites in the differentially methylated regions corroborated the importance of these processes. We also conducted a methylation study on blood to identify potential biomarkers for CCC. Our data revealed 198 differentially methylated positions (DMPs) that could serve as biomarkers of the disease, of which 61 are associated with disease severity.

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Treatment with Benznidazole during the Chronic Phase of Experimental Chagas' Disease Decreases Cardiac Alterations

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.49.4.1521-1528.2005 ◽

2005 ◽

Vol 49 (4) ◽

pp. 1521-1528 ◽

Cited By ~ 162

Author(s):

Simone Garcia ◽

Carolina O. Ramos ◽

Juliana F. V. Senra ◽

Fabio Vilas-Boas ◽

Maurício M. Rodrigues ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Chagas Disease ◽

Latin American ◽

Chronic Phase ◽

Cardiac Conduction ◽

Intraventricular Conduction ◽

Conduction Disturbances ◽

Chagasic Cardiomyopathy ◽

Chronic Chagas Disease

ABSTRACT Chagas' disease, caused by Trypanosoma cruzi infection, is one of the main causes of death due to heart failure in Latin American countries. Benznidazole, the chemotherapeutic agent most often used for the treatment of chagasic patients, is highly toxic and has limited efficacy, especially in the chronic phase of the disease. In the present study we used a mouse model of chronic Chagas' disease to investigate the effects of benznidazole treatment during the chronic phase on disease progression. The hearts of benznidazole-treated mice had decreased parasitism and myocarditis compared to the hearts of untreated chagasic mice. Both groups of Trypanosoma cruzi-infected mice had significant alterations in their electrocardiograms compared to those of the healthy mice. However, untreated mice had significantly higher cardiac conduction disturbances than benznidazole-treated mice, including intraventricular conduction disturbances, atrioventricular blocks, and extrasystoles. The levels of antibodies against T. cruzi antigens (epimastigote extract, P2β, and trans-sialidase) as well as antibodies against peptides of the second extracellular loops of β1-adrenergic and M2-muscarinic cardiac receptors were also lower in the sera from benznidazole-treated mice than in the sera from untreated mice. These results demonstrate that treatment with benznidazole in the chronic phase of infection prevents the development of severe chronic cardiomyopathy, despite the lack of complete parasite eradication. In addition, our data highlight the role of parasite persistence in the development of chronic Chagas' disease and reinforce the importance of T. cruzi elimination in order to decrease or prevent the development of severe chagasic cardiomyopathy.

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Faculty Opinions recommendation of Drug-induced cure drives conversion to a stable and protective CD8+ T central memory response in chronic Chagas disease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1107065.576411 ◽

2008 ◽

Author(s):

Thomas W von Geldern

Keyword(s):

Chagas Disease ◽

Central Memory ◽

Drug Induced ◽

Memory Response ◽

Chronic Chagas Disease

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Effects of repetitive stress during the acute phase ofTrypanosoma cruziinfection on chronic Chagas' disease in rats

Stress ◽

10.1080/10253890802168648 ◽

2009 ◽

Vol 12 (2) ◽

pp. 144-151 ◽

Cited By ~ 1

Author(s):

Leony Cristina Caetano ◽

Vânia Brazão ◽

Marina Del Vecchio Filipin ◽

Fabricia Helena Santello ◽

Luana Naiara Caetano ◽

...

Keyword(s):

Chagas Disease ◽

Acute Phase ◽

Repetitive Stress ◽

Chronic Chagas Disease

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Ficolin‐3 in chronic Chagas disease: Low serum levels associated with the risk of cardiac insufficiency

Parasite Immunology ◽

10.1111/pim.12829 ◽

2021 ◽

Author(s):

Kárita Cláudia Freitas Lidani ◽

Fabiana Antunes Andrade ◽

Marcia Holsbach Beltrame ◽

Indira Chakravarti ◽

Maria Regina Tizzot ◽

...

Keyword(s):

Chagas Disease ◽

Serum Levels ◽

Cardiac Insufficiency ◽

Chronic Chagas Disease ◽

Low Serum

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Serological Diagnosis of Chronic Chagas Disease: Is It Time for a Change?

Journal of Clinical Microbiology ◽

10.1128/jcm.00142-16 ◽

2016 ◽

Vol 54 (6) ◽

pp. 1566-1572 ◽

Cited By ~ 32

Author(s):

Alba Abras ◽

Montserrat Gállego ◽

Teresa Llovet ◽

Silvia Tebar ◽

Mercedes Herrero ◽

...

Keyword(s):

Chagas Disease ◽

False Positive ◽

Disease Diagnosis ◽

Cross Reactivity ◽

Human Migration ◽

Serological Diagnosis ◽

Content Type ◽

New Generation ◽

Single Technique ◽

Chronic Chagas Disease

Chagas disease has spread to areas that are nonendemic for the disease with human migration. Since no single reference standard test is available, serological diagnosis of chronic Chagas disease requires at least two tests. New-generation techniques have significantly improved the accuracy of Chagas disease diagnosis by the use of a large mixture of recombinant antigens with different detection systems, such as chemiluminescence. The aim of the present study was to assess the overall accuracy of a new-generation kit, the Architect Chagas (cutoff, ≥1 sample relative light units/cutoff value [S/CO]), as a single technique for the diagnosis of chronic Chagas disease. The Architect Chagas showed a sensitivity of 100% (95% confidence interval [CI], 99.5 to 100%) and a specificity of 97.6% (95% CI, 95.2 to 99.9%). Five out of six false-positive serum samples were a consequence of cross-reactivity withLeishmaniaspp., and all of them achieved results of <5 S/CO. We propose the Architect Chagas as a single technique for screening in blood banks and for routine diagnosis in clinical laboratories. Only gray-zone and positive sera with a result of ≤6 S/CO would need to be confirmed by a second serological assay, thus avoiding false-positive sera and the problem of cross-reactivity withLeishmaniaspecies. The application of this proposal would result in important savings in the cost of Chagas disease diagnosis and therefore in the management and control of the disease.

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Heart rate variability: Analysis of time-domain indices in patients with chronic Chagas disease before and after an exercise program

Revista Portuguesa de Cardiologia (English Edition) ◽

10.1016/j.repce.2013.03.003 ◽

2013 ◽

Vol 32 (3) ◽

pp. 219-227 ◽

Cited By ~ 1

Author(s):

Marcus Vinicius Amaral da Silva Souza ◽

Carla Cristiane Santos Soares ◽

Juliana Rega de Oliveira ◽

Cláudia Rosa de Oliveira ◽

Paloma Hargreaves Fialho ◽

...

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Chagas Disease ◽

Time Domain ◽

Exercise Program ◽

Heart Rate Variability Analysis ◽

Variability Analysis ◽

Before And After ◽

Chronic Chagas Disease

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Evolution of anti-Trypanosoma cruzi antibody production in patients with chronic Chagas disease: Correlation between antibody titers and development of cardiac disease severity

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0005796 ◽

2017 ◽

Vol 11 (7) ◽

pp. e0005796 ◽

Cited By ~ 8

Author(s):

Ingebourg Georg ◽

Alejandro Marcel Hasslocher-Moreno ◽

Sergio Salles Xavier ◽

Marcelo Teixeira de Holanda ◽

Eric Henrique Roma ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Disease Severity ◽

Chagas Disease ◽

Antibody Production ◽

Cardiac Disease ◽

Antibody Titers ◽

Chronic Chagas Disease

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Genome-wide analysis of long non-coding RNAs (lncRNAs) in two contrasting soybean genotypes subjected to phosphate starvation

BMC Genomics ◽

10.1186/s12864-021-07750-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Jinyu Zhang ◽

Huanqing Xu ◽

Yuming Yang ◽

Xiangqian Zhang ◽

Zhongwen Huang ◽

...

Keyword(s):

Growth And Yield ◽

Biological Processes ◽

Rna Seq ◽

Plant Growth And Development ◽

P Deficiency ◽

Genome Wide ◽

Low Phosphorus ◽

Soybean Genotypes ◽

Non Coding Rnas ◽

Sensitive Genotype

Abstract Background Phosphorus (P) is essential for plant growth and development, and low-phosphorus (LP) stress is a major factor limiting the growth and yield of soybean. Long noncoding RNAs (lncRNAs) have recently been reported to be key regulators in the responses of plants to stress conditions, but the mechanism through which LP stress mediates the biogenesis of lncRNAs in soybean remains unclear. Results In this study, to explore the response mechanisms of lncRNAs to LP stress, we used the roots of two representative soybean genotypes that present opposite responses to P deficiency, namely, a P-sensitive genotype (Bogao) and a P-tolerant genotype (NN94156), for the construction of RNA sequencing (RNA-seq) libraries. In total, 4,166 novel lncRNAs, including 525 differentially expressed (DE) lncRNAs, were identified from the two genotypes at different P levels. GO and KEGG analyses indicated that numerous DE lncRNAs might be involved in diverse biological processes related to phosphate, such as lipid metabolic processes, catalytic activity, cell membrane formation, signal transduction, and nitrogen fixation. Moreover, lncRNA-mRNA-miRNA and lncRNA-mRNA networks were constructed, and the results identified several promising lncRNAs that might be highly valuable for further analysis of the mechanism underlying the response of soybean to LP stress. Conclusions These results revealed that LP stress can significantly alter the genome-wide profiles of lncRNAs, particularly those of the P-sensitive genotype Bogao. Our findings increase the understanding of and provide new insights into the function of lncRNAs in the responses of soybean to P stress.

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