An RNA‐Binding Protein RBMS1 Promotes Endothelial Cell Autophagy to Maintain Vascular Homeostasis and Suppress Deep Vein Thrombosis

Deep vein thrombosis (DVT) is a prevalent vascular disorder characterized by aberrant coagulation within the deep venous system, and the roles of RNA-binding proteins (RBPs) in its pathogenesis remain largely undefined. Herein, using a murine inferior vena cava (IVC) stenosis model, we identify RNA-binding motif single-stranded interacting protein 1 (RBMS1) as a previously unrecognized regulator of DVT progression via the modulation of vascular endothelial cell (VEC) autophagy. By utilizing endothelial cell-conditional Rbms1 knockout mice, we demonstrate that RBMS1 deficiency exacerbates thrombus formation and impairs VEC function. Mechanistically, RBMS1 associates with autophagy-related 3 (ATG3) mRNA through its 3'-untranslated region (3'-UTR) and enhances its stability, thereby promoting autophagic flux in VECs. RBMS1 depletion destabilizes ATG3 mRNA, leading to suppressed autophagy and compromised endothelial homeostasis. Conversely, ATG3 overexpression rescues autophagy impairment and mitigates thrombotic phenotypes upon RBMS1 depletion. Collectively, our findings in the IVC stenosis-induced DVT model demonstrate that RBMS1 regulates ATG3 to maintain vascular endothelial integrity, providing a mechanistic basis for further evaluation of RBMS1 in DVT intervention.