Evidence map›Paper›PMID 42127187›Full record

ArticleScience advances2026

Preemptive cardioprotection with a small molecule in rodents that suppresses genes predictive of heart failure.

Yue Li, Matthew V Andrews, David T Humphreys, Eric Lam, Christopher J O'Keeffe, Michaella N Albao, Zuhayr Jafri, Mark J Raftery, Ling Zhong, Connor H O'Meara and 6 more

Abstract read
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In one paragraph

Article in Science advances, 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

16 authors.

Yue LiVascular Biology and Translational Research, School of Biomedical Sciences, Department of Pathology, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia.ORCID 0000-0002-5304-9188
Matthew V AndrewsAustralian Genome Research Facility, Victorian Comprehensive Cancer Centre, Melbourne, VIC 3000, Australia.
David T HumphreysBiomedical Data Science Facility, Innovation Centre, Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia.ORCID 0000-0003-4140-0089
Eric LamGarvan Genomics Platform, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.ORCID 0009-0009-8488-511X
Christopher J O'KeeffeGarvan Genomics Platform, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.ORCID 0009-0008-6395-1256
Michaella N AlbaoVascular Biology and Translational Research, School of Biomedical Sciences, Department of Pathology, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia.ORCID 0009-0003-0324-801X
Zuhayr JafriVascular Biology and Translational Research, School of Biomedical Sciences, Department of Pathology, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia.ORCID 0009-0002-3092-9104
Mark J RafteryBioanalytical Mass Spectrometry Facility, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, NSW 2052, Australia.ORCID 0000-0001-8530-2814
Ling ZhongBioanalytical Mass Spectrometry Facility, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, NSW 2052, Australia.ORCID 0000-0003-3657-4092
Connor H O'MearaVascular Biology and Translational Research, School of Biomedical Sciences, Department of Pathology, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia.
Iveta SlapetovaKatharina Gaus Light Microscopy Facility, University of New South Wales, Sydney, NSW 2052, Australia.
Maria KashermanKatharina Gaus Light Microscopy Facility, University of New South Wales, Sydney, NSW 2052, Australia.ORCID 0000-0003-0169-7578
Vaibhao JanbandhuSchool of Clinical Medicine, University of New South Wales, UNSW Sydney, Kensington, NSW 2033, Australia.ORCID 0000-0002-3837-1865
Ravinay BhindiDepartment of Cardiology, Royal North Shore Hospital and University of Sydney, St. Leonards, NSW 2065, Australia.
Peter LibbyCenter for Interdisciplinary Cardiovascular Sciences, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-1502-502X
Levon M KhachigianVascular Biology and Translational Research, School of Biomedical Sciences, Department of Pathology, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia.ORCID 0000-0003-3446-0323

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ischemic heart disease is a leading cause of death worldwide. While percutaneous coronary intervention (PCI) restores blood flow in acute coronary syndrome (ACS), reperfusion injury exacerbates myocardial damage, contributing to heart failure (HF). Preemptive administration of a cardioprotective agent could help counter the imminent proinflammatory insult of PCI and reperfusion. Administering BT2, a small-molecule MAPK kinase/extracellular signal-regulated kinase inhibitor, 24 hours before and during ischemia in rats before reperfusion reduced infarct size by ~70% and preserved cardiac function 24 hours and 2 weeks postinjury. BT2 prevented adverse left ventricular remodeling and scarring. Single nucleus RNA sequencing (snRNA-seq) and bulk RNA-seq revealed that BT2 modulated genes associated with inflammation, fibrosis, and matrix production, especially within macrophages and myofibroblasts. BT2 suppressed macrophage and neutrophil infiltration. BT2 reduced the expression of genes in rodent hearts predictive of HF in patients with ACS, including many encoding cytokines, inflammasome components, and damage-associated molecular patterns. BT2 is a small molecule that can prevent myocardial ischemia-reperfusion injury, improve heart function, reduce cardiac fibrosis, and favorably modulate multiple key genes and biological processes in rats prognostic of HF when delivered before reperfusion. This strategy could be evaluated with high-risk unstable angina/non-ST-segment elevation myocardial infarction patients or those having an elective PCI.

Indexed as

Cardiotonic AgentsGene Expression RegulationHeart FailureAnimalsDisease Models, AnimalHumansMacrophagesMaleMyocardial Reperfusion InjuryRatsCardiotonic Agents

Identifiers

PMID42127187
PMCPMC13170658

What OpenQuestion holds

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LicenceCC BY-NC
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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.