Evidence mapPaperPMID 41667113Full record

ArticleEuropean heart journal2026

Macrophage-specific circular RNA circHIPK2, inflammation, and fibrosis after myocardial infarction.

Mira Jung, Arne Schmidt, Marida Sansonetti, Bashar Al Soodi, Sabrina Thum, Angelika Pfanne, Annette Just, Ke Xiao, Cheng-Kai Huang, Sergej Erschow and 16 more

Abstract read
In one paragraph

Article in European heart journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

26 authors.

Mira JungInstitute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
Arne SchmidtInstitute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
Marida SansonettiInstitute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
Bashar Al SoodiInstitute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
Sabrina ThumInstitute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
Angelika PfanneInstitute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
Annette JustInstitute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
Ke XiaoInstitute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
Cheng-Kai HuangInstitute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
Sergej ErschowDepartment of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.ORCID 0009-0004-9586-0202
Melanie Ricke-HochDepartment of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.ORCID 0000-0001-5479-2275
Lea OehlsenInstitute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
Wilson AgyapongInstitute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
Karina JansenInstitute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
Jonas BlumeInstitute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
Gwen BüchlerInstitute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
Erika HilboldInstitute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
Christian BärInstitute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
Natalie WeberInstitute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
Maximilian SchinkePreclinical Pharmacology and Toxicology, Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Nikolai-Fuchs-Straße 1, Hannover 30625, Germany.
Ariane Hai Ha NguyenDepartment of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
Kai C WollertDepartment of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
James T ThackerayDepartment of Nuclear Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.ORCID 0000-0002-9031-100X
Frank BengelDepartment of Nuclear Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
Nico LachmannPreclinical Pharmacology and Toxicology, Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Nikolai-Fuchs-Straße 1, Hannover 30625, Germany.
Thomas ThumInstitute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.ORCID 0000-0003-4360-1511

Funding

Deutsche Forschungsgemeinschaft (DFG) JU 3222/2-1DFG HI 842/12-1European Research Council 852178European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program 852178REBIRTH 'Förderung aus Mitteln des Niedersächsischen Vorab'
6 · The paper itself

Abstract

BACKGROUND AND

aimsCardiac remodelling following MI is intricately linked to macrophage polarization dynamics, yet the underlying mechanisms remain incompletely elucidated. In this study, circHIPK2, a novel circRNA, was identified as being upregulated in inflammatory cardiac macrophages following MI. Its expression correlated with post-MI inflammation dynamics, suggesting a regulatory role in macrophage polarization. It was hypothesized that circHIPK2 functions as a molecular switch of macrophage polarization during MI progression.

methodsTo test this hypothesis, circHIPK2 levels were modulated in vitro using siRNA and overexpression vectors. A murine MI model with macrophage-targeted inhibition of circHIPK2 through AAV9-mediated shRNA delivery was employed. Cardiac function was evaluated using echocardiography, histology, and PET imaging. An ex vivo co-culture platform incorporating living myocardial slices from heart failure patients and circHIPK2-modulated human iPSC-derived macrophages was established to explore a translational potential.

resultsCircHIPK2 interacts with its binding partner G3BP1 to promote stress granule formation in macrophages. This interaction initiates a downstream inflammatory cascade, highlighting its role in immune regulation. Inhibition of circHIPK2 suppressed inflammatory signalling and reduced pro-inflammatory cytokine secretion. In a mouse model of MI, macrophage-specific inhibition of circHIPK2 improved cardiac function, reshaped the inflammatory environment, and attenuated fibrosis progression. Silencing circHIPK2 in human macrophages demonstrated therapeutic potential in established heart failure, promoting beneficial cardiac healing.

conclusionsTargeting circHIPK2 in macrophages may represent a promising therapeutic strategy for treating inflammatory cardiac conditions and heart failure, potentially leading to the development of RNA-based therapies targeting immune cells in MI treatment.

Indexed as

Intracellular Signaling Peptides and ProteinsMacrophagesMyocardial InfarctionRNA, CircularAnimalsDisease Models, AnimalFibrosisHumansInflammationMaleMiceMice, Inbred C57BLMyocardiumVentricular RemodelingIntracellular Signaling Peptides and ProteinsRNA, CircularCircular RNAImmune therapyInflammationMacrophagesMyocardial infarctionRNA therapy

Identifiers

PMID41667113
PMCPMC13247189

What Socratic holds

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LicenceCC BY
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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 Socratic graph.