Evidence map›Paper›PMID 34001623›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

Roles of KLF4 and AMPK in the inhibition of glycolysis by pulsatile shear stress in endothelial cells.

Yue Han, Ming He, Traci Marin, Hui Shen, Wei-Ting Wang, Tzong-Yi Lee, Hsiao-Chin Hong, Zong-Lai Jiang, Theodore Garland, John Y-J Shyy and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
2.8field-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

38 citing papers in PubMed, 51 citations in OpenAlex.

  1. Article
  2. Review
  3. Single-Cell Metabolic Imaging Reveals Glycogen-Driven Adaptations in Endothelial Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  4. Review
  5. Review
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  8. Review
  9. Article
  10. Article
  11. METTL3 mediates atheroprone flow-induced glycolysis in endothelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  12. SilencingInternational journal of molecular sciences · 2025
    Article
  13. Article
  14. Wall shear stress modulates metabolic pathways in endothelial cells.Metabolomics : Official journal of the Metabolomic Society · 2025
    Article
  15. Review
  16. Review
  17. Article
  18. Review
  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

12 authors at 5 institutions in 2 countries.

Yue HanInstitute of Mechanobiology and Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.ORCID 0000-0002-1362-4897
Ming HeDepartment of Medicine, University of California San Diego, La Jolla, CA 92093.
Traci MarinDepartment of Health Sciences, Victor Valley College, Victorville, CA 92395.
Hui ShenDepartment of Medicine, University of California San Diego, La Jolla, CA 92093.
Wei-Ting WangDepartment of Medicine, University of California San Diego, La Jolla, CA 92093.
Tzong-Yi LeeWarshel Institute for Computational Biology, School of Life and Health Sciences, The Chinese University of Hong Kong, Shenzhen, 999077, China.
Hsiao-Chin HongWarshel Institute for Computational Biology, School of Life and Health Sciences, The Chinese University of Hong Kong, Shenzhen, 999077, China.
Zong-Lai JiangInstitute of Mechanobiology and Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.ORCID 0000-0002-1749-8939
Theodore GarlandDepartment of Evolution, Ecology, and Organismal Biology, University of California, Riverside, CA 92521.ORCID 0000-0002-7916-3552
John Y-J ShyyDepartment of Medicine, University of California San Diego, La Jolla, CA 92093; jshyy@ucsd.edu brendan.gongol@ucr.edu shuchien@ucsd.edu.ORCID 0000-0002-5625-753X
Brendan GongolDepartment of Medicine, University of California San Diego, La Jolla, CA 92093; jshyy@ucsd.edu brendan.gongol@ucr.edu shuchien@ucsd.edu.
Shu ChienInstitute of Engineering in Medicine, University of California San Diego, La Jolla, CA 92093; jshyy@ucsd.edu brendan.gongol@ucr.edu shuchien@ucsd.edu.ORCID 0000-0003-0332-285X
University of California San Diego · USChinese University of Hong Kong, Shenzhen · CNShanghai Jiao Tong University · CNVictor Valley College · USUniversity of California, Riverside · 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
Shear Regulation of MicroRNA Transportomes and Targetomes in Vascular HomeostasisR01HL106579 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHIEN, SHU, SHYY, JOHN YJ · 2011 to 2022
$8.3M
Training in the Next Generation in Respiratory ScienceT32HL134632 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MALHOTRA, ATUL, POWELL, FRANK L. · 2017 to 2021
$2.1M
NHLBI NIH HHS R01 HL106579NHLBI NIH HHS R01 HL108735NHLBI NIH HHS T32 HL134632
6 · The paper itself

Abstract

Vascular endothelial cells (ECs) sense and respond to hemodynamic forces such as pulsatile shear stress (PS) and oscillatory shear stress (OS). Among the metabolic pathways, glycolysis is differentially regulated by atheroprone OS and atheroprotective PS. Studying the molecular mechanisms by which PS suppresses glycolytic flux at the epigenetic, transcriptomic, and kinomic levels, we have demonstrated that glucokinase regulatory protein (GCKR) was markedly induced by PS in vitro and in vivo, although PS down-regulates other glycolysis enzymes such as hexokinase (HK1). Using next-generation sequencing data, we identified the binding of PS-induced Krüppel-like factor 4 (KLF4), which functions as a pioneer transcription factor, binding to the GCKR promoter to change the chromatin structure for transactivation of GCKR. At the posttranslational level, PS-activated AMP-activated protein kinase (AMPK) phosphorylates GCKR at Ser-481, thereby enhancing the interaction between GCKR and HK1 in ECs. In vivo, the level of phosphorylated GCKR Ser-481 and the interaction between GCKR and HK1 were increased in the thoracic aorta of wild-type AMPKα2

Indexed as

Epigenesis, GeneticAdaptor Proteins, Signal TransducingAMP-Activated Protein KinasesAnimalsAorta, ThoracicBiomechanical PhenomenaGlycolysisHexokinaseHumansHuman Umbilical Vein Endothelial CellsKruppel-Like Factor 4MaleMiceMice, TransgenicPromoter Regions, GeneticProtein BindingAdaptor Proteins, Signal TransducingAMP-Activated Protein KinasesGCKR protein, humanHexokinaseHK1 protein, humanKLF4 protein, humanKruppel-Like Factor 4Prkaa2 protein, mouseAMPKepigeneticsGCKRglycolysisKLF4

Identifiers

PMID34001623
PMCPMC8166073
OpenAlexW3161491611

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.