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Updated: Aug 31, 2025

Human Saphenous Vein Endothelial Cell Isolation and Exposure to Controlled Levels of Shear Stress and Stretch
Published on: April 21, 2023
KLF4 recruits SWI/SNF to increase chromatin accessibility and reprogram the endothelial enhancer landscape under
Jan-Renier Moonen1,2,3,4, James Chappell5, Minyi Shi5
1Vera Moulton Wall Center for Pulmonary Vascular Diseases, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Abstract:
Physiologic laminar shear stress (LSS) induces an endothelial gene expression profile that is vasculo-protective. In this report, we delineate how LSS mediates changes in the epigenetic landscape to promote this beneficial response. We show that under LSS, KLF4 interacts with the SWI/SNF nucleosome remodeling complex to increase accessibility at enhancer sites that promote the expression of homeostatic endothelial genes. By combining molecular and computational approaches we discover enhancers that loop to promoters of KLF4- and LSS-responsive genes that stabilize endothelial cells and suppress inflammation, such as BMPR2, SMAD5, and DUSP5. By linking enhancers to genes that they regulate under physiologic LSS, our work establishes a foundation for interpreting how non-coding DNA variants in these regions might disrupt protective gene expression to influence vascular disease.
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