Evidence map›Paper›PMID 41664919›Full record

ArticleCirculation research2026

Cardiac Macrophages and Fibroblasts Modulate Atrial Fibrillation Maintenance.

Ana Simon-Chica, Jorge G Quintanilla, Carlos Torroja, Marinela Couselo-Seijas, Haruka Toda, Peter Lee, Alberto Benguria, Concepción Revilla, Andrés Redondo-Rodríguez, José Manuel Alfonso-Almazán and 22 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

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

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

32 authors.

Ana Simon-ChicaNovel Arrhythmogenic Mechanisms Program, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain (A.S.-C., J.G.Q., M.C.-S., H.T., A.R.-R., J.M.A.-A., A.G.-E., M.M.-B., G.L.R., C.M., D.F.-R.).
Jorge G QuintanillaNovel Arrhythmogenic Mechanisms Program, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain (A.S.-C., J.G.Q., M.C.-S., H.T., A.R.-R., J.M.A.-A., A.G.-E., M.M.-B., G.L.R., C.M., D.F.-R.).ORCID 0000-0002-2227-3507
Carlos TorrojaBioinformatics Unit, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain (C.T., F.S.-C.).ORCID 0000-0001-8914-3400
Marinela Couselo-SeijasNovel Arrhythmogenic Mechanisms Program, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain (A.S.-C., J.G.Q., M.C.-S., H.T., A.R.-R., J.M.A.-A., A.G.-E., M.M.-B., G.L.R., C.M., D.F.-R.).ORCID 0000-0001-6548-477X
Haruka TodaNovel Arrhythmogenic Mechanisms Program, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain (A.S.-C., J.G.Q., M.C.-S., H.T., A.R.-R., J.M.A.-A., A.G.-E., M.M.-B., G.L.R., C.M., D.F.-R.).ORCID 0000-0001-8054-8700
Peter LeeEssel Research and Development Inc., Toronto, Canada (P.L.).ORCID 0000-0002-0901-0999
Alberto BenguriaGenomics Unit, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain (A.B., A.D.).ORCID 0000-0002-5536-566X
Concepción RevillaDepartamento de Biotecnología, Centro Nacional Instituto de Investigación y Tecnología Agraria y Alimentaria (INIA-CSIC), Madrid, Spain (C.R., J.D.).
Andrés Redondo-RodríguezNovel Arrhythmogenic Mechanisms Program, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain (A.S.-C., J.G.Q., M.C.-S., H.T., A.R.-R., J.M.A.-A., A.G.-E., M.M.-B., G.L.R., C.M., D.F.-R.).ORCID 0000-0001-7018-0711
José Manuel Alfonso-AlmazánNovel Arrhythmogenic Mechanisms Program, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain (A.S.-C., J.G.Q., M.C.-S., H.T., A.R.-R., J.M.A.-A., A.G.-E., M.M.-B., G.L.R., C.M., D.F.-R.).ORCID 0000-0003-1233-9135
Alba García-EscolanoNovel Arrhythmogenic Mechanisms Program, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain (A.S.-C., J.G.Q., M.C.-S., H.T., A.R.-R., J.M.A.-A., A.G.-E., M.M.-B., G.L.R., C.M., D.F.-R.).ORCID 0000-0002-4649-4603
Manuel Marina-BreysseNovel Arrhythmogenic Mechanisms Program, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain (A.S.-C., J.G.Q., M.C.-S., H.T., A.R.-R., J.M.A.-A., A.G.-E., M.M.-B., G.L.R., C.M., D.F.-R.).ORCID 0000-0002-2047-1868
Carlos Galán-ArriolaMyocardial Homeostasis and Cardiac Injury Program, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain (C.G.-A., B.I.).
María Linarejos Vera-PedrosaCardiovascular Regeneration Program, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain (M.L.V.-P., J.J.).
Giulio La RosaNovel Arrhythmogenic Mechanisms Program, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain (A.S.-C., J.G.Q., M.C.-S., H.T., A.R.-R., J.M.A.-A., A.G.-E., M.M.-B., G.L.R., C.M., D.F.-R.).ORCID 0000-0001-7360-1999
Ana DopazoCentro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain (J.G.Q., M.C.-S., A.R.-R., M.M.-B., A.D., F.S.-C., B.I., E.N., D.G.-G., J.P.-V., N.P.-C., J.J., J.V., D.F.-R.).ORCID 0000-0002-4910-1684
Fátima Sánchez-CaboCentro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain (J.G.Q., M.C.-S., A.R.-R., M.M.-B., A.D., F.S.-C., B.I., E.N., D.G.-G., J.P.-V., N.P.-C., J.J., J.V., D.F.-R.).ORCID 0000-0003-1881-1664
María Jesús García-TorrentDepartment of Medicine, Universidad Complutense de Madrid, Spain (M.J.G.-T., J.P.-V).ORCID 0000-0001-5264-608X
Adriana Ortega-HernándezInstituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Laboratorio de Microbiota y Biología Vascular, Madrid, Spain (A.O.-H., D.G.-G.).ORCID 0000-0002-2654-4917
Borja IbáñezCentro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain (J.G.Q., M.C.-S., A.R.-R., M.M.-B., A.D., F.S.-C., B.I., E.N., D.G.-G., J.P.-V., N.P.-C., J.J., J.V., D.F.-R.).ORCID 0000-0002-5036-254X
Estefanía NúñezCentro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain (J.G.Q., M.C.-S., A.R.-R., M.M.-B., A.D., F.S.-C., B.I., E.N., D.G.-G., J.P.-V., N.P.-C., J.J., J.V., D.F.-R.).
Dulcenombre Gómez-GarreCentro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain (J.G.Q., M.C.-S., A.R.-R., M.M.-B., A.D., F.S.-C., B.I., E.N., D.G.-G., J.P.-V., N.P.-C., J.J., J.V., D.F.-R.).
Carlos MorilloNovel Arrhythmogenic Mechanisms Program, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain (A.S.-C., J.G.Q., M.C.-S., H.T., A.R.-R., J.M.A.-A., A.G.-E., M.M.-B., G.L.R., C.M., D.F.-R.).ORCID 0000-0002-8739-2099
Joachim GreinerInstitute for Experimental Cardiovascular Medicine, University Heart Center Freiburg-Bad Krozingen, Medical Center-University of Freiburg and Faculty of Medicine, University of Freiburg, Germany (J.G., P.K.).ORCID 0000-0001-5454-2962
Peter KohlInstitute for Experimental Cardiovascular Medicine, University Heart Center Freiburg-Bad Krozingen, Medical Center-University of Freiburg and Faculty of Medicine, University of Freiburg, Germany (J.G., P.K.).ORCID 0000-0003-0416-6270
Julián Pérez-VillacastínCentro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain (J.G.Q., M.C.-S., A.R.-R., M.M.-B., A.D., F.S.-C., B.I., E.N., D.G.-G., J.P.-V., N.P.-C., J.J., J.V., D.F.-R.).ORCID 0000-0002-4867-3912
Nicasio Pérez-CastellanoCentro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain (J.G.Q., M.C.-S., A.R.-R., M.M.-B., A.D., F.S.-C., B.I., E.N., D.G.-G., J.P.-V., N.P.-C., J.J., J.V., D.F.-R.).ORCID 0000-0003-0359-939X
José JalifeCentro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain (J.G.Q., M.C.-S., A.R.-R., M.M.-B., A.D., F.S.-C., B.I., E.N., D.G.-G., J.P.-V., N.P.-C., J.J., J.V., D.F.-R.).ORCID 0000-0003-0080-3500
Javier DomínguezDepartamento de Biotecnología, Centro Nacional Instituto de Investigación y Tecnología Agraria y Alimentaria (INIA-CSIC), Madrid, Spain (C.R., J.D.).
Jesús VázquezCentro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain (J.G.Q., M.C.-S., A.R.-R., M.M.-B., A.D., F.S.-C., B.I., E.N., D.G.-G., J.P.-V., N.P.-C., J.J., J.V., D.F.-R.).ORCID 0000-0003-1461-5092
Manuel Carnero-AlcázarCardiac Surgery Department, Hospital Clínico San Carlos, Madrid, Spain (M.C.-A.).ORCID 0000-0001-5045-5765
David Filgueiras-RamaNovel Arrhythmogenic Mechanisms Program, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain (A.S.-C., J.G.Q., M.C.-S., H.T., A.R.-R., J.M.A.-A., A.G.-E., M.M.-B., G.L.R., C.M., D.F.-R.).ORCID 0000-0001-5909-2454

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNonmyocytes may contribute to regional adaptive changes during persistent atrial fibrillation (PsAF), favoring its perpetuation. We aimed to investigate the differential features of fibroblast and macrophage populations within individual-specific atrial regions associated with PsAF maintenance.

methodsThe study was conducted in 2 pig models of PsAF with and without infarct-related substrate (N=27 and N=27, respectively) and further validated in humans with PsAF (N=20). Sham-operated pigs (N=9), healthy animals (N=4), and patients in sinus rhythm (N=7) were used as comparative controls. In pigs, in vivo high-density instantaneous frequency modulation maps were used to identify atrial regions associated with PsAF maintenance (drivers). Regional cellular composition and phenotypic states of fibroblast and myeloid lineages were determined using flow cytometry, single-cell RNA sequencing, immunohistochemistry, and proteomic analyses. The functional relevance of driver regions was further studied in patients with symptomatic PsAF undergoing ablation. Flow cytometry and single-cell RNA sequencing analyses were performed in tissue samples of the left atrial appendage in a complementary cohort of patients with PsAF undergoing thoracoscopic-guided ablation.

resultsPsAF terminated acutely in 12 of 14 pigs undergoing mapping and ablation of driver regions. In humans, driver ablation was associated with 90% AF-freedom (on/off antiarrhythmic drugs) after 2 years of follow-up. Samples from nonablated pigs revealed a phenotypic shift towards ACTA2 (actin alpha 2)-fibroblasts and PTX3 (pentraxin 3)-fibroblasts during PsAF. Although ACTA2-fibroblasts were highly preserved in human samples, paired comparisons in pig samples showed that PTX3-fibroblasts were enriched only in driver regions. PsAF also showed changes in myeloid cells towards inflammatory profiles. However, regional analysis revealed that, in both humans and pigs with PsAF, driver regions were enriched in cardiac resident macrophages with transcriptomic and proteomic profiles favoring cardiomyocyte homeostasis and cell survival.

conclusionsPsAF shows differential regional changes in fibroblast and myeloid populations with distinctive gene signatures in areas that drive the overall arrhythmia.

Indexed as

Atrial FibrillationFibroblastsMacrophagesAnimalsDisease Models, AnimalFemaleHeart AtriaHumansMaleSwineatrial appendageatrial fibrillationfibroblastsmacrophages

Identifiers

PMID41664919
PMCPMC12986039

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.