SOX11 silence inhibits atherosclerosis progression in ApoE-deficient mice by alleviating endothelial dysfunction

Abstract

SRY-Box Transcription Factor-11 (SOX11) is a transcriptional regulatory factor that plays a crucial role in inflammatory responses. However, its involvement in atherosclerosis (AS), a cardiovascular disease driven by endothelial cell inflammation, remains unknown. This study aims to elucidate the role of SOX11 in AS. The expression of SOX11 was found to be elevated in the aortic tissue of AS mice induced by feeding ApoE-deficient mice a high-fat diet. Knockdown of SOX11 using lentiviral-mediated SOX11-specific shRNA via tail vein injection resulted in a reduction in plaque area and lipid deposition within plaques at the aortic root. Furthermore, silencing SOX11 led to decreased expression of cell adhesion factors Intercellular Cell Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1, as well as reduced levels of inflammatory factors Interleukin (IL)-6, IL-1β, and chemokine Monocyte Chemotactic Protein-1. In the human umbilical vein endothelial cells (HUVECs) induced by Tumor Necrosis Factor (TNF)-α, increased inflammation was observed at the cellular level, along with enhanced monocyte adhesion. Infection of HUVECs with lentivirus carrying specific shRNA targeting SOX11 inhibited inflammatory response. Mechanistically, chromatin immunoprecipitation (ChIP)-PCR results revealed that SOX11 bound to the promoters of downstream target genes Tumor Necrosis Factor Receptor-Associated Factor-1 (TRAF1), Cluster of Differentiation (CD)40, and CD36, positively regulating their transcription. In conclusion, SOX11 plays a pivotal role in promoting endothelial cell inflammation. Suppression of SOX11 reduces endothelial cell inflammation by inhibiting the transcription of TRAF1, CD40, and CD36, thereby impeding the progression of atherosclerosis.