Evidence map›Paper›PMID 32865093›Full record

ArticleJournal of the American Heart Association2020

Histone Acetyltransferase p300 Inhibitor Improves Coronary Flow Reserve in SIRT3 (Sirtuin 3) Knockout Mice.

Han Su, Heng Zeng, Xiaochen He, Shai-Hong Zhu, Jian-Xiong Chen

Open access · goldAbstract read
In one paragraph

Article in Journal of the American Heart Association, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

28 citing papers in PubMed, 44 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Epigenetic Mechanisms in Heart Diseases.Reviews in cardiovascular medicine · 2025
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  10. Mouse Cardiovascular Imaging.Current protocols · 2024
    Review
  11. Epigenetic regulation of sex dimorphism in cardiovascular health.Canadian journal of physiology and pharmacology · 2024
    Review
  12. Article
  13. Article
  14. Review
  15. Review
  16. EP300 as a Molecular Integrator of Fibrotic Transcriptional Programs.International journal of molecular sciences · 2023
    Review
  17. Article
  18. Article
  19. Review
  20. 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

5 authors at 2 institutions in 2 countries.

Han SuDepartment of Pharmacology and Toxicology University of Mississippi Medical Center Jackson MS.
Heng ZengDepartment of Pharmacology and Toxicology University of Mississippi Medical Center Jackson MS.
Xiaochen HeDepartment of Pharmacology and Toxicology University of Mississippi Medical Center Jackson MS.
Shai-Hong ZhuDepartment of General Surgery Third Xiangya Hospital Central South University Changsha China.
Jian-Xiong ChenDepartment of Pharmacology and Toxicology University of Mississippi Medical Center Jackson MS.
University of Mississippi Medical Center · USCentral South University · CN

Funding

Regulation of vascular maturation/regression in diabetesR01HL102042 · NHLBI · VANDERBILT UNIVERSITY · PI CHEN, JIAN-XIONG · 2010 to 2020
$3.0M
NHLBI NIH HHS R01 HL102042
6 · The paper itself

Abstract

Background Coronary microvascular dysfunction is common in patients of myocardial infarction with non-obstructive coronary artery disease. Coronary flow reserve (CFR) reflects coronary microvascular function and is a powerful independent index of coronary microvascular dysfunction and heart failure. Our previous studies showed that knockout of SIRT3 (Sirtuin 3) decreased CFR and caused a diastolic dysfunction. Few studies focus on the treatment of impaired CFR and heart failure. In the present study, we explored the role of C646, a histone acetyltransferase p300 inhibitor, in regulating CFR and cardiac remodeling in SIRT3 knockout (SIRT3KO) mice. Methods and Results After treating with C646 for 14 days, CFR, pulse-wave velocity, and cardiac function were measured in SIRT3KO mice. SIRT3KO mice treated with C646 showed a significant improvement of CFR, pulse-wave velocity, ejection fraction, and fractional shortening. Treatment with C646 reversed pre-existing cardiac fibrosis, hypertrophy, and capillary rarefaction in SIRT3KO mice. Mechanistically, knockout of Sirtuin 3 resulted in significant increases in p300 expression and H3K56 acetylation. Treatment with C646 significantly reduced levels of p300 and H3K56 acetylation in SIRT3KO mice. Furthermore, treatment with C646 increased endothelial nitric oxide synthase expression and reduced arginase II expression and activity. The expression of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and VCAM-1 (vascular cell adhesion molecule 1) was also significantly suppressed by C646 treatment in SIRT3KO mice. Conclusions C646 treatment attenuated p300 and H3K56 acetylation and improved arterial stiffness and CFR via improvement of endothelial cell (EC) dysfunction and suppression of NF-κB.

Indexed as

AnimalsBenzoatesBlotting, WesternCoronary CirculationEchocardiographyFluorescent Antibody TechniqueMaleMiceMice, KnockoutMicrovesselsNitrobenzenesp300-CBP-Associated Factorp300-CBP Transcription FactorsPyrazolesPyrazolonesSirtuin 34-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acidBenzoatesNitrobenzenesp300-CBP-Associated Factorp300-CBP Transcription FactorsPyrazolesPyrazolonesSirt3 protein, mouseSirtuin 3C646coronary flow reservecoronary microvascular diseaseH3K56 acetylationp300

Identifiers

PMID32865093
PMCPMC7727016
OpenAlexW3082569921

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.