Evidence map›Paper›PMID 41988707›Full record

ArticleCirculation2026

Targeting Interleukin-8-Mediated Cellular Crosstalk Reverses Hypertrophic Cardiomyopathy and Cardiac Fibrosis in Noonan Syndrome.

Jakob Fell, Mario G Pavez-Giani, Fabian Koitka, George Kensah, Gabriela Leao Santos, Emiel P C van der Vorst, Christof Lenz, Gabriela Salinas, Alexandra Victoria Busley, Alisa Fedorenko and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 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. Article
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

17 authors.

Jakob Fell *Departments of Cardiology and Pneumology (J.F., M.G.P.-G., F.K., A.V.B., A.F., R.H., G.H., L.C.), University Medical Center Göttingen, Göttingen, Germany.
Mario G Pavez-Giani *Departments of Cardiology and Pneumology (J.F., M.G.P.-G., F.K., A.V.B., A.F., R.H., G.H., L.C.), University Medical Center Göttingen, Göttingen, Germany.
Fabian Koitka *Departments of Cardiology and Pneumology (J.F., M.G.P.-G., F.K., A.V.B., A.F., R.H., G.H., L.C.), University Medical Center Göttingen, Göttingen, Germany.ORCID 0009-0007-5226-9676
George KensahCardiothoracic and Vascular Surgery (G.K.), University Medical Center Göttingen, Göttingen, Germany.ORCID 0000-0003-0219-8279
Gabriela Leao SantosInstitute of Pharmacology and Toxicology (G.L.S., S.L., W.-H.Z.), University Medical Center Göttingen, Göttingen, Germany.ORCID 0000-0001-7253-9855
Emiel P C van der VorstDepartment of Internal Medicine I, Aachen-Maastricht Institute for Cardio-Renal Disease, and Institute for Molecular Cardiovascular Research, University Hospital Aachen, RWTH Aachen University, Aachen, Germany (E.P.C.v.d.V.).ORCID 0000-0001-5771-6278
Christof LenzClinical Chemistry (C.L.), University Medical Center Göttingen, Göttingen, Germany.ORCID 0000-0002-0946-8166
Gabriela SalinasNext-Generation Sequencing Integrative Genomics Core Unit (G.S.), University Medical Center Göttingen, Göttingen, Germany.ORCID 0000-0001-8269-2669
Alexandra Victoria BusleyDepartments of Cardiology and Pneumology (J.F., M.G.P.-G., F.K., A.V.B., A.F., R.H., G.H., L.C.), University Medical Center Göttingen, Göttingen, Germany.
Alisa FedorenkoDepartments of Cardiology and Pneumology (J.F., M.G.P.-G., F.K., A.V.B., A.F., R.H., G.H., L.C.), University Medical Center Göttingen, Göttingen, Germany.ORCID 0009-0008-1090-2477
Robin HindmarshDepartments of Cardiology and Pneumology (J.F., M.G.P.-G., F.K., A.V.B., A.F., R.H., G.H., L.C.), University Medical Center Göttingen, Göttingen, Germany.
Cordula Maria WolfDepartment of Pediatric Cardiology and Congenital Heart Disease, German Heart Center Munich, Technical University Munich, Munich, Germany (C.M.W.).ORCID 0000-0003-4701-5843
Susanne LutzInstitute of Pharmacology and Toxicology (G.L.S., S.L., W.-H.Z.), University Medical Center Göttingen, Göttingen, Germany.ORCID 0000-0002-0554-8070
Gerd HasenfussDepartments of Cardiology and Pneumology (J.F., M.G.P.-G., F.K., A.V.B., A.F., R.H., G.H., L.C.), University Medical Center Göttingen, Göttingen, Germany.
Wolfram-Hubertus ZimmermannInstitute of Pharmacology and Toxicology (G.L.S., S.L., W.-H.Z.), University Medical Center Göttingen, Göttingen, Germany.ORCID 0000-0003-1190-4040
Bernd WollnikInstitute of Human Genetics (A.F., B.W.), University Medical Center Göttingen, Göttingen, Germany.ORCID 0000-0003-2589-0364
Lukas CyganekDepartments of Cardiology and Pneumology (J.F., M.G.P.-G., F.K., A.V.B., A.F., R.H., G.H., L.C.), University Medical Center Göttingen, Göttingen, Germany.ORCID 0000-0001-9120-1382

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGenetic variants in components or regulators of the RAS-mitogen-activated protein kinase (RAS-MAPK) signaling pathway are causative for severe and early-onset hypertrophic cardiomyopathy (HCM) in patients with Noonan syndrome (NS). Despite paracrine communication being considered to play a pivotal role in the etiology of cardiomyopathies, there is a paucity of knowledge about the underlying pathomechanism that leads to the development of HCM and cardiac fibrosis in NS.

methodsTo dissect the impact of noncardiomyocytes in the development of NS, we employed two-dimensional and three-dimensional human induced pluripotent stem cell models of

resultsOur findings revealed that cytokine-mediated cellular crosstalk between cardiac fibroblasts and cardiomyocytes, predominantly activated in the disease state, serves as a primary driver of the disease. Cardiac fibroblast-specific IL-8 (interleukin-8) secretion induced fibrosis-related signatures, tissue stiffness, cardiomyocyte hypertrophy, and hypercontractility, identifying dysregulated IL-8 as a heart-autonomous signaling molecule independent of inflammation and immune cell involvement. Inhibition of IL-8-CXCR1 signaling by reparixin reversed the pathological effects in cardiac fibroblasts and cardiomyocytes.

conclusionsThese data provide evidence that targeting aberrant IL-8-CXCR1 signaling may be an effective therapeutic option for patients with NS-associated HCM.

Indexed as

Cardiomyopathy, HypertrophicInterleukin-8Myocytes, CardiacNoonan SyndromeCell CommunicationCells, CulturedFibroblastsFibrosisHumansInduced Pluripotent Stem CellsSignal TransductionCXCL8 protein, humanInterleukin-8cardiomyocytescytokineshypertrophic cardiomyopathyinduced pluripotent stem cellsinterleukin-8Noonan syndromeparacrine communication

Identifiers

PMID41988707
PMCPMC13641254

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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.