Unleashing the Potential: Myeloid-Specific STING Inhibition Mitigates Deep Vein Thrombosis
Deep vein thrombosis (DVT), the third most common cause of cardiovascular deaths, is characterized by intravascular clot formation, often accompanied by inflammation. Although the Stimulator of Interferon Genes (STING) signaling pathway has gained recognition as a central mediator of inflammation in the context of infection, cellular stress, and tissue, its intricate involvement in DVT remains enigmatic. Here, we demonstrate that STING inhibition via specific inhibitors or myeloid-specific STING deficiency ameliorated thrombus formation in murine DVT models. Furthermore, our findings uncover a direct interaction between STING and YBX1, resulting in nuclear translocation and enhanced thrombotic inflammation. A synthetic peptide, C-ST16, designed to resemble STING inhibitors, exhibits promising therapeutic potential by effectively reducing thrombus formation and diminishing inflammatory factor expression without the hepatorenal toxicity. Overall, these findings shed light on the interplay between myeloid specific STING-YBX1 and inflammation, offering novel therapeutic insights for DVT management. Overall design: To measure the alterations in gene expression levels in inferior vena cava (IVC) ligated for 24 hours in mKO mice compared to control mice. We then pefromed gene expression profiling analysis using data obtained from RNA-seq of  thrombi containing IVCs in Stingf/f mice and Stingf/f Lyzm-Cre+/- mice. Since the thrombi was too small to extract enough RNA, three thrombi was mixed as a sample and 3 samples  were included in each group.