Evidence map›Paper›PMID 42530461›Full record

ArticleThe Journal of infectious diseases2026

Integrated Methylome and Transcriptome Analysis in Chronic Chagas Cardiomyopathy Uncovers Alterations in Heart Development.

Francisco Heredia-Fernández, Javier Martínez-López, Laura C Terrón-Camero, Desiré Casares-Marfil, Pau Bosch-Nicolau, Israel Molina, Javier Martín, Marialbert Acosta-Herrera

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Article in The Journal of infectious diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Francisco Heredia-FernándezDepartment of Cell Biology and Immunology, Institute of Parasitology and Biomedicine López-Neyra, CSIC, Granada, Spain.ORCID 0009-0009-0968-2240
Javier Martínez-LópezDepartment of Cell Biology and Immunology, Institute of Parasitology and Biomedicine López-Neyra, CSIC, Granada, Spain.ORCID 0000-0003-0184-9543
Laura C Terrón-CameroDepartment of Cell Biology and Immunology, Institute of Parasitology and Biomedicine López-Neyra, CSIC, Granada, Spain.
Desiré Casares-MarfilDivision of Rheumatology, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA.
Pau Bosch-NicolauInfectious Diseases Department, Vall d'Hebron University Hospital, International Health Unit Vall d'Hebron-Drassanes, PROSICS Barcelona, Barcelona, Spain.ORCID 0000-0002-7435-1829
Israel MolinaInfectious Diseases Department, Vall d'Hebron University Hospital, International Health Unit Vall d'Hebron-Drassanes, PROSICS Barcelona, Barcelona, Spain.ORCID 0000-0001-6642-7515
Javier MartínDepartment of Cell Biology and Immunology, Institute of Parasitology and Biomedicine López-Neyra, CSIC, Granada, Spain.
Marialbert Acosta-HerreraDepartment of Cell Biology and Immunology, Institute of Parasitology and Biomedicine López-Neyra, CSIC, Granada, Spain.ORCID 0000-0002-9868-6535

Funding

Chagas Genetics CYTED Network
6 · The paper itself

Abstract

backgroundChagas disease, caused by Trypanosoma cruzi, remains a health concern worldwide. Its most severe clinical outcome, chronic Chagas cardiomyopathy (CCC), is marked by progressive cardiac dysfunction. Biological mechanisms underlying the differential development of CCC remain unclear. We hypothesized that alterations in the host DNA methylation and its influence on gene expression may contribute to this differential disease progression.

methodsWe analyzed whole-blood methylation data from 42 CCC patients and 23 individuals with the indeterminate form, followed by an integrated transcriptomic analysis in a 22 individuals subset. We performed transcription factor (TF) and functional enrichment analyses to identify biological mechanisms underlying CCC severity.

resultsSevere CCC patients exhibited higher methylation variability, particularly in immune regulation genes. Integrated analysis revealed dysregulation of genes regulating cardiac development, morphogenesis, and ion homeostasis, with GATA5 as a key TF regulating cardiac pathways. TF activity inferred from peripheral blood resembled cardiac signatures previously described, with RUNX TFs, key drivers of Th1 immune polarization, correlating strongly with disease severity.

conclusionsOur findings highlight a systemic epigenetic signature in blood that reflects cardiac pathology in CCC. These insights advance our understanding of CCC pathogenesis and facilitate novel blood-based biomarkers and therapeutic targets aimed at preventing disease progression.

Indexed as

Chagas CardiomyopathyDNA MethylationEpigenomeHeartAdultChronic DiseaseFemaleGene Expression ProfilingHumansMaleMiddle AgedTranscription FactorsTranscriptomeTrypanosoma cruziTranscription Factorsbiomarkerschronic Chagas cardiomyopathyepigeneticstranscription factors

Identifiers

PMID42530461
PMCPMC13600374

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.