Evidence map›Paper›PMID 40534567›Full record

ArticleCirculation. Heart failure2025

Cardiac-Targeted AAV5-S100A1 Gene Therapy Protects Against Adverse Remodeling and Contractile Dysfunction in Postischemic Hearts.

Dorothea Kehr, Janek Salatzki, Birgit Seger, Karl Varadi, Jennifer Birkenstock, Philipp Schlegel, Erhe Gao, Walter J Koch, Hugo A Katus, Norbert Frey and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation. Heart failure, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. 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

18 authors.

Dorothea KehrDivision of Molecular and Translational Cardiology (D.K., B.S., K.V., J.B., A.J., M.B., J. Ritterhoff, P.M.), University Hospital Heidelberg, Germany.
Janek SalatzkiDepartment of Internal Medicine III (D.K., J.S., B.S., K.V., J.B., P.S., H.A.K., N.F., J. Riffel, F.A., A.J., J. Ritterhoff, P.M.), University Hospital Heidelberg, Germany.ORCID 0000-0003-1421-474X
Birgit SegerDivision of Molecular and Translational Cardiology (D.K., B.S., K.V., J.B., A.J., M.B., J. Ritterhoff, P.M.), University Hospital Heidelberg, Germany.ORCID 0009-0002-2106-0005
Karl VaradiDivision of Molecular and Translational Cardiology (D.K., B.S., K.V., J.B., A.J., M.B., J. Ritterhoff, P.M.), University Hospital Heidelberg, Germany.
Jennifer BirkenstockDivision of Molecular and Translational Cardiology (D.K., B.S., K.V., J.B., A.J., M.B., J. Ritterhoff, P.M.), University Hospital Heidelberg, Germany.
Philipp SchlegelDepartment of Internal Medicine III (D.K., J.S., B.S., K.V., J.B., P.S., H.A.K., N.F., J. Riffel, F.A., A.J., J. Ritterhoff, P.M.), University Hospital Heidelberg, Germany.ORCID 0000-0003-3888-6655
Erhe GaoCenter for Translational Medicine, Temple University, Philadelphia, PA (E.G., W.J.K.).
Walter J KochCenter for Translational Medicine, Temple University, Philadelphia, PA (E.G., W.J.K.).ORCID 0000-0002-8522-530X
Hugo A KatusDepartment of Internal Medicine III (D.K., J.S., B.S., K.V., J.B., P.S., H.A.K., N.F., J. Riffel, F.A., A.J., J. Ritterhoff, P.M.), University Hospital Heidelberg, Germany.ORCID 0000-0002-2293-2314
Norbert FreyDepartment of Internal Medicine III (D.K., J.S., B.S., K.V., J.B., P.S., H.A.K., N.F., J. Riffel, F.A., A.J., J. Ritterhoff, P.M.), University Hospital Heidelberg, Germany.ORCID 0000-0001-7611-378X
Johannes RiffelDepartment of Internal Medicine III (D.K., J.S., B.S., K.V., J.B., P.S., H.A.K., N.F., J. Riffel, F.A., A.J., J. Ritterhoff, P.M.), University Hospital Heidelberg, Germany.
Florian AndréDepartment of Internal Medicine III (D.K., J.S., B.S., K.V., J.B., P.S., H.A.K., N.F., J. Riffel, F.A., A.J., J. Ritterhoff, P.M.), University Hospital Heidelberg, Germany.ORCID 0000-0003-1428-2611
Karsten PeppelLCC, King of Prussia, PA (K.P.).ORCID 0009-0003-0394-6176
Andreas JungmannDivision of Molecular and Translational Cardiology (D.K., B.S., K.V., J.B., A.J., M.B., J. Ritterhoff, P.M.), University Hospital Heidelberg, Germany.
Martin BuschDivision of Molecular and Translational Cardiology (D.K., B.S., K.V., J.B., A.J., M.B., J. Ritterhoff, P.M.), University Hospital Heidelberg, Germany.ORCID 0000-0002-2717-7063
Helga PfannkucheInstitute of Veterinary Physiology, Faculty of Veterinary Medicine, Leipzig University, Germany (H.P.).
Julia RitterhoffDivision of Molecular and Translational Cardiology (D.K., B.S., K.V., J.B., A.J., M.B., J. Ritterhoff, P.M.), University Hospital Heidelberg, Germany.ORCID 0000-0002-3419-4830
Patrick MostDivision of Molecular and Translational Cardiology (D.K., B.S., K.V., J.B., A.J., M.B., J. Ritterhoff, P.M.), University Hospital Heidelberg, Germany.ORCID 0000-0002-3604-2419

Funding

Targeting Pathways Involved in Cardiac Injury for Novel Repair StrategiesP01HL147841 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI ELROD, JOHN WILLIAM · 2020 to 2024
$11.4M
Targeting GRK2 in the HeartR01HL061690 · NHLBI · THOMAS JEFFERSON UNIVERSITY · PI KOCH, WALTER J. · 1998 to 2022
$4.2M
NHLBI NIH HHS P01 HL147841NHLBI NIH HHS R01 HL061690
6 · The paper itself

Abstract

backgroundGuided by long-term safety data for AAV5 (adeno-associated virus 5) in humans, our translational study investigated whether AAV5 effectively delivers genes to healthy and achieves therapeutic efficacy in dysfunctional human-sized hearts, using a clinically applicable mode of administration and vector dosages.

methodsAAV-mediated cardiac gene transfer in pigs was performed by percutaneous catheter-based retrograde intravenous vector delivery, and vector genome and transgene expression levels determined by reverse transcription-polymerase chain reaction and immunoblotting. Postmyocardial infarction (MI) cardiac dysfunction porcine and murine models were generated by coronary catheter-based occlusion and ligation, respectively. The study end points left ventricular ejection fraction and left ventricular MI size, were measured by cardiac magnetic resonance imaging and echocardiography. Bulk myocardial RNA-sequencing and weighted gene correlation network analysis were used to link study end points to molecular pathway mechanisms. Safety was assessed by clinical chemistry, blood count and ECG.

resultsIn a first biodistribution study, AAV5 (1×10

conclusionsProviding the clinically relevant proof of concept for AAV5 to effectively transduce healthy and dysfunctional human-sized hearts, its clinical long-term safety, scalable producibility, and low preexisting immunity in humans may predestine AAV5 as an effective and safe gene carrier for a prevalent disease such as chronic heart failure, using therapeutic genetic effectors such as

Indexed as

DependovirusGenetic TherapyMyocardial ContractionMyocardial InfarctionS100 ProteinsVentricular Function, LeftVentricular RemodelingAnimalsDisease Models, AnimalGenetic VectorsGene Transfer TechniquesHumansMaleMiceMyocardiumStroke VolumeS100A1 proteinS100 Proteinsanimalscathetersheart failureswinetissue distribution

Identifiers

PMID40534567
PMCPMC12278446

What OpenQuestion holds

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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 OpenQuestion graph.