Myeloid-Specific STING-YBX1 Interaction Alleviates Coagulation in Deep Vein Thrombosis

Area of Science:

• Immunology
• Cardiovascular Biology
• Molecular Medicine

Background:

• Deep vein thrombosis (DVT) is a major cause of cardiovascular death, characterized by clot formation and inflammation.
• The role of the STING (stimulator of interferon genes) signaling pathway in DVT pathogenesis is not well understood.
• STING is known to mediate inflammatory responses in various conditions, but its specific involvement in DVT requires elucidation.

Purpose of the Study:

• To investigate the role of myeloid cell-intrinsic STING signaling in the progression of deep vein thrombosis (DVT).
• To evaluate the therapeutic potential of STING inhibitors, including a novel synthetic peptide, in managing DVT.
• To explore the interaction between STING and Y-box-binding protein 1 (YBX1) in the context of DVT.

Main Methods:

• Utilized murine models of DVT to study the effects of STING inhibition.
• Employed STING inhibitors and genetic depletion of myeloid-specific STING to assess thrombus formation.
• Conducted biochemical analyses to investigate the STING-YBX1 interaction and tested a synthetic peptide (C-ST16) for therapeutic efficacy.

Main Results:

• Myeloid cell-specific STING signaling was identified as a key driver of DVT progression.
• STING inhibition significantly reduced thrombus formation in murine DVT models.
• A direct interaction between STING and YBX1 was observed, leading to nuclear translocation and increased thrombotic inflammation. The peptide C-ST16 effectively reduced thrombus and inflammation without toxicity.

Conclusions:

• Myeloid-specific STING-YBX1 signaling critically drives inflammation in DVT progression.
• STING inhibitors, especially the synthetic peptide C-ST16, show promise as a therapeutic strategy for DVT.
• Targeted inhibition of STING offers novel insights for developing anti-inflammatory therapies for thrombotic disorders.