Evidence map›Paper›PMID 23754392›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2013

Ca2+/calmodulin-dependent protein kinase kinase β phosphorylation of Sirtuin 1 in endothelium is atheroprotective.

Liang Wen, Zhen Chen, Fan Zhang, Xiaopei Cui, Wei Sun, Greg G Geary, Yinsheng Wang, David A Johnson, Yi Zhu, Shu Chien and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 1 pooled it
4.1field-weighted citation impact, top 7% 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

47 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Occludin: a gatekeeper of brain Infection by HIV-1.Fluids and barriers of the CNS · 2023
    Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Molecular Mechanisms Underlying CaInternational journal of molecular sciences · 2022
    Review
  18. Review
  19. Review
  20. Article
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

11 authors at 5 institutions in 3 countries.

Liang WenDepartment of Physiology and Pathophysiology, Peking University Health Sciences Center, Beijing 100191, China.
Zhen Chen
Fan Zhang
Xiaopei Cui
Wei Sun
Greg G Geary
Yinsheng Wang
David A Johnson
Yi Zhu
Shu Chien
John Y-J Shyy
Institute of Biomedical Science · GBPeking University · CNUniversity of California, Riverside · USCalifornia State University, San Bernardino · USUniversity of California San Diego · US

Funding

Systems Biology Analyses for Hemodynamic Regulation of Vascular HomeostasisR01HL108735 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHIEN, SHU, SHYY, JOHN YJ · 2012 to 2024
$13.4M
Chemistry and Biology of DNA CarboxyalkylationR01DK082779 · NIDDK · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI WANG, YINSHENG · 2009 to 2016
$3.0M
Shear Stress, AMPK, and Endothelial FunctionsR01HL089940 · NHLBI · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI SHYY, JOHN YJ · 2009 to 2013
$1.9M
Shear stress, SIRT1, and Arterial StiffeningR01HL105318 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SHYY, JOHN YJ · 2010 to 2013
$1.5M
NHLBI NIH HHS HL105318NHLBI NIH HHS HL108735NHLBI NIH HHS HL89940NHLBI NIH HHS R01 HL089940NHLBI NIH HHS R01 HL105318NHLBI NIH HHS R01 HL108735NIDDK NIH HHS DK82779NIDDK NIH HHS R01 DK082779
6 · The paper itself

Abstract

Atheroprotective flow exerts antioxidative and anti-inflammatory effects on vascular endothelial cells (ECs), in part through the induction of Sirtuin 1 (SIRT1), a class III histone deacetylase. The role of Ca(2+)/calmodulin-dependent protein kinase kinase (CaMKK)β in flow induction of SIRT1 both in vitro and in vivo was investigated. Pulsatile shear stress mimicking atheroprotective flow increased the level of SIRT1 in cultured ECs by enhancing its stability, and this effect was abolished by inhibition or knockdown of CaMKKβ. Flow-enhanced SIRT1 stability was primarily mediated by CaMKKβ phosphorylation of SIRT1 at Ser-27 and Ser-47, as evidenced by in vitro kinase assay, mass spectrometry, and experiments using loss- or gain-of-function SIRT1 mutants. Flow-induced CaMKKβ phosphorylation of SIRT1 Ser-27 and Ser-47 increased antioxidative and anti-inflammatory capacities. Ablation of CaMKKβ or SIRT1 in mice with an apolipoprotein E-null background showed increased atherosclerosis both in athero-prone and in athero-protective areas. The results suggest that the CaMKKβ-SIRT1 axis in ECs is mechanosensitive, antioxidative, and anti-inflammatory.

Indexed as

Amino Acid SequenceAnimalsApolipoproteins EAtherosclerosisCalcium-Calmodulin-Dependent Protein Kinase KinaseEndothelium, VascularGene Knockdown TechniquesHumansHuman Umbilical Vein Endothelial CellsMiceMice, Inbred C57BLMice, KnockoutMolecular Sequence DataPhosphorylationProtein StabilityPulsatile FlowApolipoproteins ECalcium-Calmodulin-Dependent Protein Kinase KinaseSIRT1 protein, humanSirt1 protein, mouseSirtuin 1

Identifiers

PMID23754392
PMCPMC3696824
OpenAlexW2066674982

What OpenQuestion holds

Textmetadata
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.