Evidence map›Paper›PMID 39970910›Full record

ArticleCell systems2025

Cold and hot fibrosis define clinically distinct cardiac pathologies.

Shoval Miyara, Miri Adler, Kfir B Umansky, Daniel Häußler, Elad Bassat, Yalin Divinsky, Jacob Elkahal, David Kain, Daria Lendengolts, Ricardo O Ramirez Flores and 23 more

Abstract read
In one paragraph

Article in Cell systems, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

  1. Review
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  5. Pareto optimality reveals an atlas of cellular archetypes.Proceedings of the National Academy of Sciences of the United States of America · 2026
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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

33 authors.

Shoval MiyaraDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Miri AdlerTananbaum Center for Theoretical and Analytical Human Biology, Yale University School of Medicine, New Haven, CT, USA.
Kfir B UmanskyDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Daniel HäußlerTUM School of Medicine and Health, Institute of Experimental Oncology and Therapy Research, Technical University of Munich, Munich, Germany.
Elad BassatResearch Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Vienna, Austria.
Yalin DivinskyDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Jacob ElkahalDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
David KainDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Daria LendengoltsDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Ricardo O Ramirez FloresHeidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Heidelberg, Germany.
Hanna Bueno-LevyDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Ofra GolaniDepartment of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel.
Tali ShalitThe Mantoux Bioinformatics institute of the Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel.
Michael GershovitsThe Mantoux Bioinformatics institute of the Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel.
Eviatar WeizmanThe Mantoux Bioinformatics institute of the Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel.
Alexander GenzelinakhDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Danielle M KimchiDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Avraham ShakkedDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Lingling ZhangDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Jingkui WangResearch Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Vienna, Austria.
Andrea BaehrKlinik und Poliklinik für Innere Medizin I, University Clinic rechts der Isar, Technical University of Munich, Munich, Germany; DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
Zachary PetroverDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Rachel SarigDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Tatjana DornFirst Department of Medicine, Cardiology, Klinikum rechts der Isar, Technical University of Munich, School of Medicine and Health, Munich, Germany.
Alessandra MorettiDZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany; First Department of Medicine, Cardiology, Klinikum rechts der Isar, Technical University of Munich, School of Medicine and Health, Munich, Germany.
Julio Saez-RodriguezHeidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Heidelberg, Germany; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, Cambridgeshire, UK.
Christian KupattKlinik und Poliklinik für Innere Medizin I, University Clinic rechts der Isar, Technical University of Munich, Munich, Germany; DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
Elly M TanakaResearch Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Vienna, Austria.
Ruslan MedzhitovTananbaum Center for Theoretical and Analytical Human Biology, Yale University School of Medicine, New Haven, CT, USA; Howard Hughes Medical Institute, Department of Immunobiology, Yale University School of Medicine, Yale, New Haven, CT, USA.
Achim KrügerTUM School of Medicine and Health, Institute of Experimental Oncology and Therapy Research, Technical University of Munich, Munich, Germany.
Avi MayoDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Uri AlonDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. Electronic address: uri.alon@weizmann.ac.il.
Eldad TzahorDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. Electronic address: eldad.tzahor@weizmann.ac.il.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Fibrosis remains a major unmet medical need. Simplifying principles are needed to better understand fibrosis and to yield new therapeutic approaches. Fibrosis is driven by myofibroblasts that interact with macrophages. A mathematical cell-circuit model predicts two types of fibrosis: hot fibrosis driven by macrophages and myofibroblasts and cold fibrosis driven by myofibroblasts alone. Testing these concepts in cardiac fibrosis resulting from myocardial infarction (MI) and heart failure (HF), we revealed that acute MI leads to cold fibrosis whereas chronic injury (HF) leads to hot fibrosis. MI-driven cold fibrosis is conserved in pigs and humans. We computationally identified a vulnerability of cold fibrosis: the myofibroblast autocrine growth factor loop. Inhibiting this loop by targeting TIMP1 with neutralizing antibodies reduced myofibroblast proliferation and fibrosis post-MI in mice. Our study demonstrates the utility of the concepts of hot and cold fibrosis and the feasibility of a circuit-to-target approach to pinpoint a treatment strategy that reduces fibrosis. A record of this paper's transparent peer review process is included in the supplemental information.

Indexed as

Heart FailureMyocardial InfarctionAnimalsFibrosisHumansMacrophagesMiceMyocardiumMyofibroblastsSwineTissue Inhibitor of Metalloproteinase-1Tissue Inhibitor of Metalloproteinase-1autocrine loopcold fibrosisfibrosisheart failurehot fibrosismacrophagemyocardial infarctionmyofibroblastregenerationTIMP1

Identifiers

PMID39970910
PMCPMC11922821

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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 OpenQuestion graph.