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

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. 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. 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. The cGAS-STING pathway, as a key cytosolic DNA-sensing mechanism, can regulate immune cell infiltration and induce vascular cell dysfunction, thereby driving pathological vascular remodeling in cardiovascular diseases such as pulmonary arterial hypertension, atherosclerosis, and aortic dissection. The canonical and non-canonical cGAS-STING signaling pathways interact with pathways including TLRs, Hippo-YAP, and BMP, forming a complex regulatory network during vascular remodeling. Therapeutic strategies that target the cGAS-STING pathway using small-molecule inhibitors and combine with nanodelivery technologies have shown certain therapeutic potential in alleviating vascular inflammation and remodeling. Current research gaps include insufficient understanding of cell-specific mechanisms and the roles of non-canonical pathways. At the same time, single-cell technologies and nanomedicine are expected to provide new directions for the precise modulation of this pathway in the treatment of cardiovascular diseases.