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

• DOI: 10.1073/pnas.2103982118
• Publication Date: 2021-05-17T20:37:25Z
• Authors: 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; Brendan Gongol; Shu Chien
• Keywords: Hexokinase

Significance This work identifies mechanotransduction mechanisms by which blood flow regulates glycolysis in vascular endothelium. We demonstrate that atheroprotective pattern decreases glycolysis, an energy-demanding metabolic process, endothelium vitro and vivo. GCKR, inhibitor of glycolytic flux, is up-regulated flow, contrast to the down-regulation other genes. As a pioneer transcription factor induced KLF4 epigenetically remodels GCKR promoter thus transactivates GCKR. At posttranslational level, flow–activated AMPK phosphorylates hence increases binding hexokinase, key enzyme glycolysis. The translational significance these findings builds on identification animal model with high level voluntary wheel running.