CREB1 Silencing Protects Against Inflammatory Response in Rats with Deep Vein Thrombosis Through Reducing RPL9 Expression and Blocking NF-κB Signaling.

Abstract

Apoptosis and inflammation of vascular endothelial cells (VECs) are the most important causes of deep vein thrombosis (DVT). cAMP response element binding protein 1 (CREB1) encodes a transcription factor that binds as a homodimer to the cAMP-responsive element and can promote inflammation. CREB1 is found to be upregulated in the plasma of patients with venous thromboembolism. However, the biological functions of CREB1 in DVT remain unknown. We evaluated the effect of CREB1 in a rat model of inferior vena cava (IVA) stenosis-induced DVT. IVC stenosis resulted in stable thrombus, inflammatory response and CREB1 upregulation, whereas CREB1 knockdown inhibited thrombus and inflammation in DVT rats. In vitro analysis showed that CREB1 knockdown inhibited VEC apoptosis. Mechanistically, CREB1 knockdown reduced Ribosomal protein L9 (RPL9) expression and blocked the NF-κB pathway. Therefore, CREB1 may become a potential therapeutic target of DVT prevention.