Evidence map›Paper›PMID 37905452›Full record

ArticleCirculation2023

Reduced Mitochondrial Protein Translation Promotes Cardiomyocyte Proliferation and Heart Regeneration.

Feng Gao, Tian Liang, Yao Wei Lu, Linbin Pu, Xuyang Fu, Xiaoxuan Dong, Tingting Hong, Feng Zhang, Ning Liu, Yuxia Zhou and 13 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
8.2field-weighted citation impact, top 2% of its field
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

39 citing papers in PubMed, 53 citations in OpenAlex.

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  11. Targeting Arterial Dysfunction in Cardiovascular Disease Using Stem Cell-Based Therapies.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Review
  12. An Integrated Evaluation Framework for Adult Heart Regeneration.Journal of cellular and molecular medicine · 2026
    Article
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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

23 authors at 6 institutions in 3 countries.

Feng Gao *Department of Cardiology, State Key Laboratory of Transvascular Implantation Devices, Provincial Key Lab of Cardiovascular Research, Second Affiliated Hospital (F.G., T.L., L.P., X.F., X.D., T.H., F.Z., N.L., H.Y., W.Z., X.H., J.W., J.C.).
Tian Liang *Department of Cardiology, State Key Laboratory of Transvascular Implantation Devices, Provincial Key Lab of Cardiovascular Research, Second Affiliated Hospital (F.G., T.L., L.P., X.F., X.D., T.H., F.Z., N.L., H.Y., W.Z., X.H., J.W., J.C.).ORCID 0000-0002-1563-516X
Yao Wei Lu *Department of Cardiology (Y.W.L., W.T.P., D.-Z.W.), Boston Children's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0001-6200-2974
Linbin PuDepartment of Cardiology, State Key Laboratory of Transvascular Implantation Devices, Provincial Key Lab of Cardiovascular Research, Second Affiliated Hospital (F.G., T.L., L.P., X.F., X.D., T.H., F.Z., N.L., H.Y., W.Z., X.H., J.W., J.C.).
Xuyang FuDepartment of Cardiology, State Key Laboratory of Transvascular Implantation Devices, Provincial Key Lab of Cardiovascular Research, Second Affiliated Hospital (F.G., T.L., L.P., X.F., X.D., T.H., F.Z., N.L., H.Y., W.Z., X.H., J.W., J.C.).
Xiaoxuan DongDepartment of Cardiology, State Key Laboratory of Transvascular Implantation Devices, Provincial Key Lab of Cardiovascular Research, Second Affiliated Hospital (F.G., T.L., L.P., X.F., X.D., T.H., F.Z., N.L., H.Y., W.Z., X.H., J.W., J.C.).ORCID 0000-0002-3712-3720
Tingting HongDepartment of Cardiology, State Key Laboratory of Transvascular Implantation Devices, Provincial Key Lab of Cardiovascular Research, Second Affiliated Hospital (F.G., T.L., L.P., X.F., X.D., T.H., F.Z., N.L., H.Y., W.Z., X.H., J.W., J.C.).
Feng ZhangDepartment of Cardiology, State Key Laboratory of Transvascular Implantation Devices, Provincial Key Lab of Cardiovascular Research, Second Affiliated Hospital (F.G., T.L., L.P., X.F., X.D., T.H., F.Z., N.L., H.Y., W.Z., X.H., J.W., J.C.).
Ning LiuDepartment of Cardiology, State Key Laboratory of Transvascular Implantation Devices, Provincial Key Lab of Cardiovascular Research, Second Affiliated Hospital (F.G., T.L., L.P., X.F., X.D., T.H., F.Z., N.L., H.Y., W.Z., X.H., J.W., J.C.).
Yuxia ZhouInstitute of Translational Medicine, Zhejiang University School of Medicine (F.G., T.L., L.P., X.F., X.D., F.Z., N.L., Y.Z., H.W., P.L., J.C.).
Hongkun WangInstitute of Translational Medicine, Zhejiang University School of Medicine (F.G., T.L., L.P., X.F., X.D., F.Z., N.L., Y.Z., H.W., P.L., J.C.).
Ping LiangInstitute of Translational Medicine, Zhejiang University School of Medicine (F.G., T.L., L.P., X.F., X.D., F.Z., N.L., Y.Z., H.W., P.L., J.C.).ORCID 0000-0001-6806-3735
Yuxuan GuoInstitute of Cardiovascular Sciences, Peking University Health Science Center, Beijing, China (Y.G.).ORCID 0000-0002-6009-4403
Hong YuDepartment of Cardiology, State Key Laboratory of Transvascular Implantation Devices, Provincial Key Lab of Cardiovascular Research, Second Affiliated Hospital (F.G., T.L., L.P., X.F., X.D., T.H., F.Z., N.L., H.Y., W.Z., X.H., J.W., J.C.).
Wei ZhuDepartment of Cardiology, State Key Laboratory of Transvascular Implantation Devices, Provincial Key Lab of Cardiovascular Research, Second Affiliated Hospital (F.G., T.L., L.P., X.F., X.D., T.H., F.Z., N.L., H.Y., W.Z., X.H., J.W., J.C.).
Xinyang HuDepartment of Cardiology, State Key Laboratory of Transvascular Implantation Devices, Provincial Key Lab of Cardiovascular Research, Second Affiliated Hospital (F.G., T.L., L.P., X.F., X.D., T.H., F.Z., N.L., H.Y., W.Z., X.H., J.W., J.C.).ORCID 0000-0002-6699-8470
Hong ChenVascular Biology Program (H.C.), Boston Children's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-1906-6611
Bin ZhouState Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China (B.Z.).
William T PuDepartment of Cardiology (Y.W.L., W.T.P., D.-Z.W.), Boston Children's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-4551-8079
John D MablyCenter for Regenerative Medicine, University of South Florida Health Heart Institute, Departments of Internal Medicine and Molecular Pharmacology and Physiology, Morsani School of Medicine, University of South Florida, Tampa, FL (J.D.M., D.-Z.W.).ORCID 0000-0002-3626-9090
Jian'an WangDepartment of Cardiology, State Key Laboratory of Transvascular Implantation Devices, Provincial Key Lab of Cardiovascular Research, Second Affiliated Hospital (F.G., T.L., L.P., X.F., X.D., T.H., F.Z., N.L., H.Y., W.Z., X.H., J.W., J.C.).
Da-Zhi WangDepartment of Cardiology (Y.W.L., W.T.P., D.-Z.W.), Boston Children's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0003-1774-6549
Jinghai ChenDepartment of Cardiology, State Key Laboratory of Transvascular Implantation Devices, Provincial Key Lab of Cardiovascular Research, Second Affiliated Hospital (F.G., T.L., L.P., X.F., X.D., T.H., F.Z., N.L., H.Y., W.Z., X.H., J.W., J.C.).ORCID 0000-0002-5401-047X
Zhejiang University · CNBoston Children's Hospital · USMinistry of Public Health · MGCenter for Excellence in Molecular Cell Science · CNPeking University · CNUniversity of South Florida · US

Funding

Epsin in Angiogenesis and Vascular RemodelingR01HL093242 · NHLBI · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI CHEN, HONG, WANG, DA-ZHI · 2009 to 2021
$7.3M
Molecular Mechanisms Controlling Lymphatic Vascular Function in Health and DiseaseR01HL133216 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI CHEN, HONG, DIXON, JAMES BRANDON · 2016 to 2025
$6.7M
CD45-mediated endothelial-to-mesenchymal transition in cardiovascular diseaseR01HL141853 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI CHEN, HONG, WANG, DA-ZHI · 2020 to 2023
$3.3M
The Role of Adaptor Protein Disabled-2 in Maintaining Endothelial Cell Function in AtherosclerosisR01HL162367 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI CHEN, HONG, SHI, JINJUN · 2022 to 2025
$3.0M
Molecular Mechanisms Governing Vascular Cell Function and Phenotype in Health and DiseaseR01HL158097 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI CHEN, HONG, CHEN, YABING · 2021 to 2024
$3.0M
MOLECULAR MECHANISMS OF DYSTROPHIC CARDIOMYOPATHYR01HL149401 · NHLBI · UNIVERSITY OF SOUTH FLORIDA · PI WANG, DA-ZHI · 2019 to 2022
$2.3M
Function and Mechanism of the Intercalated Disc Protein XinB in Cardiomyocyte Proliferation and Cardiac RegenerationR01HL168900 · NHLBI · UNIVERSITY OF SOUTH FLORIDA · PI Da-Zhi Wang · 2023 to 2026
$2.2M
lncRNA Function and Mechanisms during Cardiac Development and DiseaseR01HL165794 · NHLBI · UNIVERSITY OF SOUTH FLORIDA · PI Da-Zhi Wang · 2023 to 2026
$2.2M
MicroRNAs, cardiac function and cardiomyopathyR01HL138757 · NHLBI · UNIVERSITY OF SOUTH FLORIDA · PI WANG, DA-ZHI · 2017 to 2020
$2.1M
Therapeutic applications of miRNAs in myocardial and cardiac regenerationR01HL125925 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI WANG, DA-ZHI · 2016 to 2019
$1.8M
Molecular Mechanisms of Dilated CardiomyopathyR01HL116919 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI WANG, DA-ZHI · 2013 to 2016
$1.7M
BLRD VA I01 BX004426NHLBI NIH HHS R01 HL093242NHLBI NIH HHS R01 HL116919NHLBI NIH HHS R01 HL125925NHLBI NIH HHS R01 HL133216NHLBI NIH HHS R01 HL138757NHLBI NIH HHS R01 HL141853NHLBI NIH HHS R01 HL149401NHLBI NIH HHS R01 HL158097NHLBI NIH HHS R01 HL162367NHLBI NIH HHS R01 HL165794NHLBI NIH HHS R01 HL168900
6 · The paper itself

Abstract

backgroundThe importance of mitochondria in normal heart function are well recognized and recent studies have implicated changes in mitochondrial metabolism with some forms of heart disease. Previous studies demonstrated that knockdown of the mitochondrial ribosomal protein S5 (MRPS5) by small interfering RNA (siRNA) inhibits mitochondrial translation and thereby causes a mitonuclear protein imbalance. Therefore, we decided to examine the effects of MRPS5 loss and the role of these processes on cardiomyocyte proliferation.

methodsWe deleted a single allele of MRPS5 in mice and used left anterior descending coronary artery ligation surgery to induce myocardial damage in these animals. We examined cardiomyocyte proliferation and cardiac regeneration both in vivo and in vitro. Doxycycline treatment was used to inhibit protein translation. Heart function in mice was assessed by echocardiography. Quantitative real-time polymerase chain reaction and RNA sequencing were used to assess changes in transcription and chromatin immunoprecipitation (ChIP) and BioChIP were used to assess chromatin effects. Protein levels were assessed by Western blotting and cell proliferation or death by histology and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays. Adeno-associated virus was used to overexpress genes. The luciferase reporter assay was used to assess promoter activity. Mitochondrial oxygen consumption rate, ATP levels, and reactive oxygen species were also analyzed.

resultsWe determined that deletion of a single allele of MRPS5 in mice results in elevated cardiomyocyte proliferation and cardiac regeneration; this observation correlates with improved cardiac function after induction of myocardial infarction. We identified ATF4 (activating transcription factor 4) as a key regulator of the mitochondrial stress response in cardiomyocytes from Mrps5

conclusionsThese data highlight a critical role for MRPS5/ATF4 in cardiomyocytes and an exciting new avenue of study for therapies to treat myocardial injury.

Indexed as

Induced Pluripotent Stem CellsMyocytes, CardiacAnimalsCell ProliferationCells, CulturedDoxycyclineHumansMiceMitochondrial ProteinsProtein BiosynthesisRegenerationRNA, Small InterferingDoxycyclineMitochondrial ProteinsRNA, Small Interferingcell divisionmitochondriamyocardial infarctionmyocytesregeneration

Identifiers

PMID37905452
PMCPMC10841688
OpenAlexW4388034217

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Registered trials

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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.