Evidence map›Paper›PMID 41487100›Full record

ArticleCirculation2026

GRSF1 Protects Against Heart Failure by Maintaining BCAA Homeostasis.

Hu Wang, Jiaxing Wang, Min Zhu, Ling Jin, Hao Cui, Cihang Liu, Chenyu Fan, Hui Li, Jichun Yang, Ming Cui and 3 more

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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 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. Review
  2. Article
  3. Review
  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

13 authors.

Hu WangDepartment of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing, China (H.W., J.W., M.Z., L.J., C.F., H.L., M.C., M.X.).ORCID 0009-0009-6913-9514
Jiaxing WangDepartment of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing, China (H.W., J.W., M.Z., L.J., C.F., H.L., M.C., M.X.).
Min ZhuDepartment of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing, China (H.W., J.W., M.Z., L.J., C.F., H.L., M.C., M.X.).ORCID 0000-0002-5902-1186
Ling JinDepartment of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing, China (H.W., J.W., M.Z., L.J., C.F., H.L., M.C., M.X.).ORCID 0000-0002-0687-9234
Hao CuiState Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (M.Z., H.C., J.S.).ORCID 0000-0003-2319-8980
Cihang LiuDepartment of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, China (C.L., W.W.).ORCID 0000-0001-8658-9247
Chenyu FanDepartment of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing, China (H.W., J.W., M.Z., L.J., C.F., H.L., M.C., M.X.).ORCID 0000-0001-7878-2629
Hui LiDepartment of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing, China (H.W., J.W., M.Z., L.J., C.F., H.L., M.C., M.X.).ORCID 0000-0002-2108-0201
Jichun YangDepartment of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China (J.Y.).ORCID 0000-0001-8150-2923
Ming CuiDepartment of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing, China (H.W., J.W., M.Z., L.J., C.F., H.L., M.C., M.X.).ORCID 0000-0002-1173-0645
Jiangping SongState Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (M.Z., H.C., J.S.).ORCID 0000-0002-9488-7823
Wengong WangDepartment of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, China (C.L., W.W.).ORCID 0000-0002-1720-809X
Ming XuDepartment of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing, China (H.W., J.W., M.Z., L.J., C.F., H.L., M.C., M.X.).ORCID 0000-0003-1680-3628

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundImbalances in cardiac branched-chain amino acid (BCAA) metabolism and mitochondrial homeostasis are implicated in the onset and development of heart failure. However, the mechanisms triggering the downregulation of cardiac BCAA metabolism in heart failure remain unclear. Here, we identify a novel role of the RNA-binding protein GRSF1 (guanine-rich RNA sequence binding factor 1) in post-transcriptionally regulating cell-intrinsic BCAA metabolic pathways, ultimately contributing to the pathogenesis of heart failure.

methodsWe examined GRSF1 expression in the heart tissues of patients with dilated cardiomyopathy and generated mice with cardiomyocyte-specific deletion or overexpression of GRSF1 in vivo to investigate its role in heart failure. The effect of GRSF1 on BCAA homeostasis was assessed through untargeted and targeted metabolomics and mitochondrial function analysis. To elucidate the mechanisms underlying GRSF1-mediated metabolic regulation, we employed mice with cardiomyocyte-specific deletion of BCKDHB (branched-chain keto acid dehydrogenase E1 subunit β) and mice with cardiomyocyte-specific expression of GRSF1 lacking a quasi-RNA recognition motif.

resultsGRSF1 expression was significantly decreased in the hearts of patients with heart failure and failing murine hearts. Cardiomyocyte-specific GRSF1 deletion resulted in cardiac dysfunction, spontaneous progression to dilated cardiomyopathy, and heart failure, accompanied by increased cardiac hypertrophy and fibrosis. Conversely, GRSF1 overexpression attenuated cardiac remodeling and heart failure induced by transverse aortic constriction. Mechanistically, GRSF1 maintained BCAA homeostasis and mitochondrial function by directly interacting with the G-tracts in the coding region of BCKDHB mRNA through a quasi-RNA recognition motif to promote the stability of BCKDHB mRNA at the post-transcriptional level, thereby increasing its protein expression. Functional recovery mediated by GRSF1 overexpression in cardiomyocytes was partially blocked upon cardiac-specific deletion of BCKDHB.

conclusionsOur study identified GRSF1 as a cell-intrinsic metabolic checkpoint that maintains cardiac BCAA homeostasis by regulating BCKDHB mRNA turnover. Targeting GRSF1 may offer therapeutic benefits for heart failure and other cardiometabolic diseases requiring BCAA manipulation.

Indexed as

Amino Acids, Branched-ChainHeart FailureRNA-Binding ProteinsAnimalsCardiomyopathy, DilatedHomeostasisHumansMaleMiceMice, Inbred C57BLMice, KnockoutMyocytes, CardiacAmino Acids, Branched-ChainRNA-Binding ProteinsBCAA metabolismGRSF1heart failureRNA-binding protein

Identifiers

PMID41487100
PMCPMC12965822

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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.