Evidence map›Paper›PMID 42855501›Full record

ArticleNature cardiovascular research2026

Human adult and pediatric multimodal transcriptomic atlas of progression from pressure-loaded to failing right ventricle.

Ivan A Kuznetsov, Kristina Li, Yasmine Guedira, Bridget Simonson, Mark Chaffin, Yonathan T Aberra, Kenneth C Bedi, Trace Thome, Yijun Yang, Kirsten Branch and 15 more

Abstract read
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In one paragraph

Article in Nature cardiovascular 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

25 authors.

Ivan A KuznetsovCardiovascular Institute, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-0023-3405
Kristina LiDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-4417-0998
Yasmine GuediraCardiovascular Disease Initiative, The Broad Institute, Cambridge, MA, USA.
Bridget SimonsonCardiovascular Disease Initiative, The Broad Institute, Cambridge, MA, USA.ORCID http://orcid.org/0009-0003-5601-0953
Mark ChaffinCardiovascular Disease Initiative, The Broad Institute, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-1234-5562
Yonathan T AberraCardiovascular Institute, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Kenneth C BediCardiovascular Institute, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-3588-9324
Trace ThomeCardiovascular Institute, University of Pennsylvania, Philadelphia, PA, USA.
Yijun YangCardiovascular Institute, University of Pennsylvania, Philadelphia, PA, USA.
Kirsten BranchCardiovascular Institute, University of Pennsylvania, Philadelphia, PA, USA.
Wencao ZhaoCardiovascular Institute, University of Pennsylvania, Philadelphia, PA, USA.
Wenkai ZhuDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Wei ZhouCardiovascular Institute, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-9607-4490
Farid F KadyrovCenter for Cardiovascular Research, Department of Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, MO, USA.
Junedh M AmruteCenter for Cardiovascular Research, Department of Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-6851-0168
Ling LaiCardiovascular Institute, University of Pennsylvania, Philadelphia, PA, USA.
Joanna GriffinCardiovascular Institute, University of Pennsylvania, Philadelphia, PA, USA.
Li LiCardiovascular Institute, University of Pennsylvania, Philadelphia, PA, USA.
Jian LiCardiovascular Institute, University of Pennsylvania, Philadelphia, PA, USA.
Shelley D MiyamotoDepartment of Pediatrics, University of Colorado Anschutz Medical Campus, Children's Hospital Colorado, Aurora, CO, USA.
Patrick EllinorCardiovascular Disease Initiative, The Broad Institute, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-2067-0533
Kenneth B MarguliesCardiovascular Institute, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-8093-4465
Kory J LavineCenter for Cardiovascular Research, Department of Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0003-1948-9945
Zoltan Arany *Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA, USA. zarany@pennmedicine.upenn.edu.ORCID http://orcid.org/0000-0003-1368-2453
Jonathan J Edwards *Cardiovascular Institute, Children's Hospital of Philadelphia, Philadelphia, PA, USA. edwardsj6@chop.edu.ORCID http://orcid.org/0000-0002-8153-7066

Funding

Integrative genomics of human heart failureR01HL105993 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI ASHLEY, EUAN A, CAPPOLA, THOMAS P. · 2011 to 2014
$8.9M
Mechanical Stress-Dependent Remodeling of the Cardiac Microtubule NetworkR01HL149891 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI Kenneth Ber Margulies, Benjamin Lears Prosser · 2020 to 2026
$4.2M
Branched chain amino acids in heart failureR01HL152446 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI Zoltan P Arany · 2020 to 2026
$3.7M
Endogenous Cardiac Repair in HumansR01HL089847 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MARGULIES, KENNETH BER · 2009 to 2012
$1.9M
Defining the Role of ROR2 in Right Ventricular Failure PathogenesisK08HL159311 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI EDWARDS, JONATHAN JOSEPH · 2021 to 2025
$657k
Computationally Driven Design of De Novo Genetically Encoded Voltage IndicatorsF30MH122076 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI KUZNETSOV, IVAN · 2020 to 2023
$151k
American Diabetes Association (ADA) ADA Award 1-25-PDF-106Children's Hospital of Philadelphia (CHOP) Frontier ProgramU.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) K08 HL159311U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01 HL089847U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01 HL105993U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01 HL149891U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01 HL152446U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) T32 HL0078U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) F30 MH122076
6 · The paper itself

Abstract

Right ventricular failure (RVF) independently predicts mortality in heart failure, yet its pathophysiology is poorly understood. Here we present a multi-modal atlas of human right ventricular pressure loading and failure, including bulk (n = 142), single-nucleus (n = 11) and Xenium spatial (n = 9) transcriptomics in adults, plus pediatric (n = 14) and mouse pulmonary artery banding cohorts. Subclustering resolved 34 cell subtypes across 12 lineages along a two-phase trajectory. Phase 1 (non-failing to pressure-loaded) accounts for most of the transcriptional change detectable by bulk and single-nucleus RNA sequencing and is marked by loss of resident macrophage identity, fibroblast activation, endothelial expansion and erosion of tissue-protective programs. Phase 2 (pressure-loaded to RVF) produces little change in bulk RNA sequencing but is resolved by spatial transcriptomics, engaging multi-lineage fibrotic, endothelial-activation and cardiomyocyte-reactivation programs, with a gain of extracellular matrix (collagen, laminin, thrombospondin) signaling over a stable cell contact adhesion baseline. Mitochondrial respirometry revealed respiratory dysfunction in adult and mouse RVF but not pediatric RVF. Multi-lineage remodeling of the cardiac microenvironment emerges as the central molecular program of RVF, meriting further study as possible disease-modifying targets.

Identifiers

What Socratic holds

Textmetadata
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 Socratic graph.