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.
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.
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Who cites it
38 citing papers in PubMed, 51 citations in OpenAlex.
- Low Shear Stress Promotes Atherosclerosis by Mediating Pathological Accumulation of Endothelial Lipid Droplets via the KLF4/TFEB/ATP1A1 Axis.Journal of cardiovascular development and disease · 2026Article
- Review
- Single-Cell Metabolic Imaging Reveals Glycogen-Driven Adaptations in Endothelial Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mechanical regulation of metabolism, epigenetics, and their interplay.npj biomedical innovations · 2026Review
- Spatial architecture of atherosclerotic plaques: coordinating immune responses through mechanotransduction and vesicular trafficking.Frontiers in cell and developmental biology · 2026Review
- Mechanical cues enhance chondrocyte function: Insights from mechanoreception, regulation, and biological responses.Mechanobiology in medicine · 2025Review
- Reconceptualizing Endothelial-to-mesenchymal transition in atherosclerosis: Signaling pathways and prospective targeting strategies.Journal of advanced research · 2025Review
- Impacts of aging and fluid shear stress on vascular endothelial metabolism and atherosclerosis development.Journal of biomedical science · 2025Review
- Laminar Flow Alters EV Composition in HUVECs: A Study of Culture Medium Optimization and Molecular Profiling of Vesicle Cargo.Small methods · 2025Article
- Caffeine enhances antitumor T-cell activity by suppressing kynurenine pathway in colorectal cancer.Nature communications · 2025Article
- METTL3 mediates atheroprone flow-induced glycolysis in endothelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- SilencingInternational journal of molecular sciences · 2025Article
- Single-cell RNA sequencing of the carotid artery and femoral artery of rats exposed to hindlimb unloading.Cellular and molecular life sciences : CMLS · 2025Article
- Wall shear stress modulates metabolic pathways in endothelial cells.Metabolomics : Official journal of the Metabolomic Society · 2025Article
- The molecular determinants regulating redox signaling in diabetic endothelial cells.Frontiers in pharmacology · 2025Review
- Glucose Metabolism Reprogramming of Vascular Endothelial Cells and Its Implication in Development of Atherosclerosis.Reviews in cardiovascular medicine · 2024Review
- ASF1A-dependent P300-mediated histone H3 lysine 18 lactylation promotes atherosclerosis by regulating EndMT.Acta pharmaceutica Sinica. B · 2024Article
- Shear Stress-Induced AMP-Activated Protein Kinase Modulation in Endothelial Cells: Its Role in Metabolic Adaptions and Cardiovascular Disease.International journal of molecular sciences · 2024Review
- Unveiling the metabolic landscape of pulmonary hypertension: insights from metabolomics.Respiratory research · 2024Review
- Shear stress and pathophysiological PI3K involvement in vascular malformations.The Journal of clinical investigation · 2024Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
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
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Registered trials
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.