Defining cardiac functional recovery in end-stage heart failure at single-cell resolution
Open accessAbstract
Recovery of cardiac function is the holy grail of heart failure therapy yet is infrequently observed and remains poorly understood. In this study, we performed single-nucleus RNA sequencing from patients with heart failure who recovered left ventricular systolic function after left ventricular assist device implantation, patients who did not recover and non-diseased donors. We identified cell-specific transcriptional signatures of recovery, most prominently in macrophages and fibroblasts. Within these cell types, inflammatory signatures were negative predictors of recovery, and downregulation of RUNX1 was associated with recovery. In silico perturbation of RUNX1 in macrophages and fibroblasts recapitulated the transcriptional state of recovery. Cardiac recovery mediated by BET inhibition in mice led to decreased macrophage and fibroblast Runx1 expression and diminished chromatin accessibility within a Runx1 intronic peak and acquisition of human recovery signatures. These findings suggest that cardiac recovery is a unique biological state and identify RUNX1 as a possible therapeutic target to facilitate cardiac recovery.
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Previous and concurrent work highlighted the functional role of this gene regulatory network in cardiac fibrosis.
“Indeed, previous and concurrent work has highlighted the functional role of this gene regulatory network in cardiac fibrosis28–30.”
From Targeting immune–fibroblast cell communication in heart failure (2024) · cites this paper as [29]
In Results (‘RUNX1 GRN is associated with recovery’; page unavailable), the paper reports that simulated RUNX1 deletion shifts fibroblasts away from states associated with fibrosis and heart failure. This supports a proposed role for the network, but the perturbation was in silico; the paper does not establish a functional role in cardiac fibrosis experimentally. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe authors previously showed expansion of RUNX1-expressing cells in human heart failure.
“we previously showed expansion of RUNX1-expressing cells in human HF29.”
From Targeting immune–fibroblast cell communication in heart failure (2024) · cites this paper as [29]
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BackgroundMethodSelf-citationFive-year outcomes following left ventricular assist device implantation in England
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Targeting immune–fibroblast cell communication in heart failure
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Self-citation
- Authors
- Amrute, J. M., Lai, L., Ma, P., Koenig, A. L., Kamimoto, K., Bredemeyer, A., Shankar, T. S., Kuppe, C., Kadyrov, F. F., Schulte, L. J., Stoutenburg, D., Kopecky, B. J., Navankasattusas, S., Visker, J., Morris, S. A., Kramann, R., Leuschner, F., Mann, D. L., Drakos, S. G., & Lavine, K. J.
- Affiliations
- Washington University in St. Louis (US)
- University of Utah (US)
- RWTH Aachen University (DE)
- Erasmus MC (NL)
- University Hospital Heidelberg (DE)
- Corresponding author
- Lavine, Kory J.
- ORCID
- Amrute, Junedh M.
- Lai, Lulu
- Ma, Pan
- Koenig, Andrew L.
- Kamimoto, Kenji
- Bredemeyer, Andrea
- Shankar, Thirupura S.
- Kuppe, Christoph
- Kadyrov, Farid F.
- Schulte, Linda J.
- Stoutenburg, Dylan
- Kopecky, Benjamin J.
- Navankasattusas, Sutip
- Visker, Joseph
- Morris, Samantha A.
- Kramann, Rafael
- Leuschner, Florian
- Mann, Douglas L.
- Drakos, Stavros G.
- Lavine, Kory J.
- Venue
- Nature Cardiovascular Research
- Published
- 2023-04-06
- Volume
- 2
- Issue
- 4
- Pages
- 399-416
- ISSN
- 2731-0590 (ISSN-L)
- PMC
- PMC10426763
- OpenAlex
- W4362664789
- Cited by
- 79
- References
- 72
- Citations by year
- 2026: 31 · 2025: 27 · 2024: 17 · 2023: 4
- FWCI
- 15.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Cardiovascular Research (publishedVersion)
- PubMed (publishedVersion)
- RWTH Publications (RWTH Aachen) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- PubMed Central (acceptedVersion)
- Funders
- American Heart Association
- Myocarditis Foundation
- U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute
- Fondation Leducq
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Physical Sciences › Engineering › Biomedical Engineering › Mechanical Circulatory Support Devices
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- cardiac function recovery, end-stage heart failure, left ventricular assist device, single-nucleus RNA sequencing, RUNX1, macrophages, cardiac fibroblasts, inflammation, BET inhibition, chromatin accessibility, left ventricular systolic function, therapeutic target
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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