Evidence map›Paper›PMID 30552062›Full record

ArticleEBioMedicine2019

HDAC inhibitor valproic acid protects heart function through Foxm1 pathway after acute myocardial infarction.

Shuo Tian, Ienglam Lei, Wenbin Gao, Liu Liu, Yijing Guo, Jeffery Creech, Todd J Herron, Shaoxiang Xian, Peter X Ma, Y Eugene Chen and 3 more

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

Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 8% 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

42 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.

  1. Pooled it
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  11. Acetylation in Cardiac Aging: Molecular Mechanism and Therapeutic Approaches.Results and problems in cell differentiation · 2025
    Review
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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

13 authors at 4 institutions in 3 countries.

Shuo TianDepartment of Cardiac Surgery, Cardiovascular Center, The University of Michigan, Ann Arbor, MI 48109, USA.
Ienglam LeiDepartment of Cardiac Surgery, Cardiovascular Center, The University of Michigan, Ann Arbor, MI 48109, USA; Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau, PR China.
Wenbin GaoDepartment of Cardiac Surgery, Cardiovascular Center, The University of Michigan, Ann Arbor, MI 48109, USA; The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510405, PR China.
Liu LiuDepartment of Cardiac Surgery, Cardiovascular Center, The University of Michigan, Ann Arbor, MI 48109, USA.
Yijing GuoDepartment of Cardiac Surgery, Cardiovascular Center, The University of Michigan, Ann Arbor, MI 48109, USA; Department of Spine Surgery, Xiangya Spinal Surgery Center, Xiangya Hospital, Central South University, Changsha 410008, China.
Jeffery CreechCardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Todd J HerronCardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Shaoxiang XianThe First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510405, PR China.
Peter X MaDepartment of Biologic and Materials Science, University of Michigan, Ann Arbor, MI 48109, USA.
Y Eugene ChenCardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Yongqing LiDepartment of Surgery, University of Michigan Health System, Ann Arbor, MI 48109, USA.
Hasan B AlamDepartment of Surgery, University of Michigan Health System, Ann Arbor, MI 48109, USA.
Zhong WangDepartment of Cardiac Surgery, Cardiovascular Center, The University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: zhongw@med.umich.edu.
University of Michigan–Ann Arbor · USFirst Affiliated Hospital of Guangzhou University of Chinese Medicine · CNMichigan Medicine · USUniversity of Macau · MO

Funding

Epigenetic control of multipotent cardiac progenitor cell differentiationR01HL109054 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WANG, ZHONG · 2012 to 2016
$1.9M
Nanofibrous self-gelling microspheres for heart regenerationR01HL139735 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MA, PETER X, WANG, ZHONG · 2019 to 2022
$1.6M
NHLBI NIH HHS R01 HL109054NHLBI NIH HHS R01 HL139735
6 · The paper itself

Abstract

backgroundEpigenetic histone acetylation is a major event controlling cell functions, such as metabolism, differentiation and repair. Here, we aim to determine whether Valproic acid (VPA), a FDA approved inhibitor of histone deacetylation for bipolar disease, could protect heart against myocardial infarction (MI) injury and elucidate key molecular pathways.

methodsVPA was administrated to MI rats at different time points, onset and after MI injury. Echocardiography, histology, serum biology assays, and gene expression, inhibition, and over-expression were performed to characterize the systolic function, infarct size, gene and signaling pathways.

findingsVPA treatment reduced the infarct size by ~50% and preserved the systolic function of heart after acute MI in rats. Even 60 min after infarction, VPA treatment significantly decreased infarct size. Furthermore, long-term treatment of VPA markedly improved myocardial performance. VPA regulated gene expression essential for cell survival and anti-inflammatory response. Consequently, oxidative stress and cell death were notably reduced after VPA treatment. Moreover, Foxm1 was identified as a potential key target of VPA. Overexpression of Foxm1 provided similar heart protective effect to VPA treatment. Particularly, both VPA treatment and Foxm1 over-expression repressed inflammatory response after MI for heart protection. In contrast, inhibition of Foxm1 activity abolished the cardiac protective effect of VPA. VPA mediated CM protection through Foxm1 upregulation was also identified in a human ESC derived CM hypoxia/reperfusion system.

interpretationVPA treatments significantly reduce cardiac damage after MI and the cardioprotective effect of VPA is likely mediated via Foxm1 pathway. FUND: This work was mainly supported by 1R01HL109054.

Indexed as

AnimalsCell HypoxiaDisease Models, AnimalForkhead Box Protein M1Gene Expression RegulationHeart Function TestsHistone Deacetylase InhibitorsHuman Embryonic Stem CellsHumansMyocardial InfarctionRatsSignal TransductionUp-RegulationValproic AcidForkhead Box Protein M1FOXM1 protein, humanHistone Deacetylase InhibitorsValproic AcidCardiomyocyte protectionFoxm1Myocardial infarctionValproic acid

Identifiers

PMID30552062
PMCPMC6354709
OpenAlexW2904770603

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.