cGAS/STING pathway emerges as key driver of inflammation, cell death, and fibrosis in Cardiovascular Diseases

Cardiovascular diseases (CVDs) remain the leading cause of global mortality and morbidity, necessitating novel therapeutic strategies. Inflammation is a pivotal factor in CVD pathogenesis, and the cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway has been increasingly implicated. This pathway recognizes both non-self and self-DNA, including mitochondrial and nuclear DNA, to activate downstream proinflammatory signaling. While circulating cell-free DNA is a known biomarker for CVDs, the precise mechanisms by which self-DNA contributes to the inflammatory signaling, cell death, and fibrosis in CVDs have been unclear.

This review synthesizes current understanding on the roles of self-DNA and the cGAS/STING pathway in the pathophysiology of Cardiovascular Diseases (CVDs). The authors examined accumulating evidence linking cGAS/STING activation to inflammation, cell death, and fibrosis in the cardiovascular system. The review specifically discusses how various pathological stressors induce self-DNA release into the cytosol and bloodstream from damaged cells, and explores the therapeutic potential of targeting this pathway to mitigate CVD progression.

The review highlights that the cGAS/STING pathway is critically involved in CVD pathogenesis by recognizing both non-self and self-DNA, including mitochondrial and nuclear DNA. This recognition activates downstream proinflammatory signaling molecules such as TANK-binding kinase 1, IFN regulatory factor 3, and NF-κB. > Accumulating evidence implicates the cGAS/STING pathway in driving inflammation, cell death, and fibrosis characteristic of CVDs. Pathological stressors in the cardiovascular system lead to self-DNA release into the cytosol and bloodstream, which serves as a useful biomarker for CVDs. The pathway's activation contributes to the inflammatory cascade and cellular damage observed in various CVDs, underscoring its central role in disease progression.