Research progress on the mechanisms of cGAS-STING signaling in immune cell infiltration associated with vascular remodeling.

BACKGROUND

Vascular remodeling is a hallmark of various cardiovascular diseases and is increasingly recognized as an immune-mediated process. Recent evidence has identified the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway as a critical mediator linking cytosolic DNA sensing to innate immune activation. Beyond its classical role in host defense against pathogens, the cGAS-STING pathway plays a pivotal role in regulating the recruitment, activation, and functional polarization of diverse immune cell populations, including macrophages, neutrophils, T cells, B cells, dendritic cells, and eosinophils, thereby contributing to vascular inflammation and pathological remodeling. MAIN TEXT: This review summarizes recent advances in understanding how cGAS-STING signaling governs immune cell infiltration and intercellular communication that underlie vascular remodeling. We also explore the direct effects of cGAS-STING activation on vascular endothelial and smooth muscle cells, and its crosstalk with other key signaling pathways such as Toll-like receptors (TLRs), Hippo-YAP, and bone morphogenetic proteins (BMPs). In addition, we discuss current and emerging therapeutic strategies targeting this pathway, including small-molecule inhibitors and combination therapies utilizing nano-delivery systems.

CONCLUSIONS

By highlighting the role of immune cell infiltration as a novel therapeutic axis, this review provides new perspectives for the modulation of vascular remodeling and the treatment of cardiovascular diseases. These insights may inform future research on pathway-specific interventions and the development of personalized therapeutic approaches.