Epigenetic changes in shear‐stressed endothelial cells

• DOI: 10.1002/cbin.12138
• Publication Date: 2024-02-29T10:19:40Z
• Authors: Thaís Silva Pinto; Geórgia da Silva....; Célio Júnior da C...; Amanda Fantini de...; Alex de Camargo C...; Simone L. Silva; Abdulwahab A. Abu...; Willian F. Zambuzzi; Rodrigo A. Foganh...
• Keywords: Histones; 0303 health sciences; 03 medical and health sciences; Human Umbilical Vein Endothelial Cells; Hemodynamics; Humans; Stress, Mechanical; Cells, Cultured; Epigenesis, Genetic

Abstract Epigenetic changes, particularly histone compaction modifications, have emerged as critical regulators in the epigenetic pathway driving endothelial cell phenotype under constant exposure to laminar forces induced by blood flow. However, underlying mechanisms governing behavior this context remain poorly understood. To address knowledge gap, we conducted vitro experiments using human umbilical vein cells subjected various tensional simulating pathophysiological flow shear stress conditions, ranging from normotensive hypertensive forces. Our study uncovers a noteworthy observation wherein exposed high demonstrate decrease marks H3K4ac and H3K27ac, accompanied significant alterations levels of HDAC (histone deacetylase) proteins. Moreover, negative regulatory effect increased on HOXA13 gene expression concomitant increase long noncoding RNA, HOTTIP, suggesting direct association with suppression HOXA13. Collectively, these findings represent first evidence role histone‐related modifications modulating chromatin during mechanosignaling response elevated Additionally, our results highlight importance understanding physiological vascular biology patients, emphasizing potential for developing small molecules modulate its activity. These warrant further preclinical investigations open new avenues therapeutic interventions targeting conditions.