Evidence map›Paper›PMID 27249230›Full record

ArticleAging2016

SIRT6 protects against endothelial dysfunction and atherosclerosis in mice.

Suowen Xu, Meimei Yin, Marina Koroleva, Michael A Mastrangelo, Wenbo Zhang, Peter Bai, Peter J Little, Zheng Gen Jin

Open access · hybridAbstract read
In one paragraph

Article in Aging, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed, 2 pooled it
4.9field-weighted citation impact, top 5% 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

64 citing papers in PubMed, 2 syntheses or guidelines pooled it, 112 citations in OpenAlex.

  1. A Meta-Analysis on the Association BetweenFrontiers in physiology · 2020
    Pooled it
  2. Pooled it
  3. Article
  4. Review
  5. Article
  6. Article
  7. Microvascular Health as a Key Determinant of Organismal Aging.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Review
  14. Acetylation in Cardiac Aging: Molecular Mechanism and Therapeutic Approaches.Results and problems in cell differentiation · 2025
    Review
  15. Sirt6 protects retinal ganglion cells and optic nerve from degeneration during aging and glaucoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Hallmarks of cardiovascular ageing.Nature reviews. Cardiology · 2023
    Review

4 more citing papers are in PubMed but not listed here.

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

8 authors at 4 institutions in 3 countries.

Suowen XuAab Cardiovascular Research Institute, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14620, USA.
Meimei YinAab Cardiovascular Research Institute, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14620, USA.
Marina KorolevaAab Cardiovascular Research Institute, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14620, USA.
Michael A MastrangeloAab Cardiovascular Research Institute, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14620, USA.
Wenbo ZhangDepartment of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA.
Peter BaiDepartment of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Peter J LittleSchool of Pharmacy, The University of Queensland, Pharmacy Australia Centre of Excellence (PACE), Woolloongabba QLD 4102, Australia.
Zheng Gen JinAab Cardiovascular Research Institute, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14620, USA.
University of Rochester · USThe University of Texas Medical Branch at Galveston · USUniversity of Debrecen · HUUniversity of Queensland · AU

Funding

SIRT6 and vascular endothelial homeostasisR01HL130167 · NHLBI · UNIVERSITY OF ROCHESTER · PI JIN, ZHENG-GEN · 2017 to 2025
$4.2M
Molecular regulation of angiogenesisR01HL114570 · NHLBI · UNIVERSITY OF ROCHESTER · PI JIN, ZHENG-GEN · 2012 to 2016
$1.9M
Regulation of angiogenesis by transcription factorsR01HL128363 · NHLBI · UNIVERSITY OF ROCHESTER · PI JIN, ZHENG-GEN · 2016 to 2019
$1.5M
Regulation of laminar flow atheroprotective genes by HDAC5R01HL109502 · NHLBI · UNIVERSITY OF ROCHESTER · PI JIN, ZHENG-GEN · 2012 to 2015
$1.5M
NHLBI NIH HHS R01 HL109502NHLBI NIH HHS R01 HL114570NHLBI NIH HHS R01 HL128363NHLBI NIH HHS R01 HL130167
6 · The paper itself

Abstract

SIRT6 is an important member of sirtuin family that represses inflammation, aging and DNA damage, three of which are causing factors for endothelial dysfunction. SIRT6 expression is decreased in atherosclerotic lesions from ApoE(-/-) mice and human patients. However, the role of SIRT6 in regulating vascular endothelial function and atherosclerosis is not well understood. Here we show that SIRT6 protects against endothelial dysfunction and atherosclerosis. Global and endothelium-specific SIRT6 knockout mice exhibited impaired endothelium-dependent vasorelaxation. Moreover, SIRT6(+/-) haploinsufficient mice fed a high-fat diet (HFD) also displayed impaired endothelium-dependent vasorelaxation. Importantly, SIRT6(+/-); ApoE(-/-) mice after HFD feeding exhibited exacerbated atherosclerotic lesion development, concurrent with increased expression of the proinflammatory cytokine VCAM-1. Loss- and gain-of-SIRT6 function studies in cultured human endothelial cells (ECs) showed that SIRT6 attenuated monocyte adhesion to ECs. RNA-sequencing profiling revealed that SIRT6 overexpression decreased the expression of multiple atherosclerosis-related genes, including proatherogenic gene TNFSF4 (tumor necrosis factor superfamily member 4). Chromatin immunoprecipitation assays showed that SIRT6 decreased TNFSF4 gene expression by binding to and deacetylating H3K9 at TNFSF4 gene promoter. Collectively, these findings demonstrate that SIRT6 play a pivotal role in maintaining endothelial function and increased SIRT6 activity could be a new therapeutic strategy to combat atherosclerotic disease.

Indexed as

AnimalsApolipoproteins EAtherosclerosisCell AdhesionCells, CulturedEndothelial CellsEndothelium, VascularHaploinsufficiencyHumansMembrane GlycoproteinsMiceMice, KnockoutOX40 LigandSirtuinsTumor Necrosis FactorsVascular Cell Adhesion Molecule-1Apolipoproteins EMembrane GlycoproteinsOX40 LigandSirt6 protein, mouseSirtuinsTnfsf4 protein, mouseTumor Necrosis FactorsVascular Cell Adhesion Molecule-1atherosclerosisendothelial dysfunctionRNA-seqSIRT6vascular inflammation

Identifiers

PMID27249230
PMCPMC4931854
OpenAlexW2415755712

What OpenQuestion holds

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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.