The cGAS/STING Pathway: Friend or Foe in Regulating Cardiomyopathy

Inflammation is a key hallmark in cardiomyopathy where misdirected immune activation causes chronic myocardial dysfunction. Among the emerging mechanisms implicated in the dysfunction, the cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) signaling pathway has attracted significant attention. Acting as a critical DNA sensor, the cGAS/STING pathway coordinates inflammatory responses triggered by microbial invasions or endogenous stressors such as autophagic or apoptotic cell death. Despite its pivotal role, the precise molecular mechanisms regulating this pathway and its contribution to aberrant inflammation in cardiomyopathy remain poorly understood and controversial. To address this scientific gap, we first summarized the key findings on the cGAS/STING pathway in different cardiomyopathies using in vivo/in vitro models as well as clinical samples. In the next step, we explored how the cGAS/STING pathway could be modulated by it agonists and antagonists in cardiomyopathy. Finally, leveraging publicly available human single-cell ribonucleic acid sequencing (RNA-seq) dataset and systematic literature review, we identified existing molecular interventions and highlighted potential therapeutic targets to mitigate cGAS/STING-driven inflammation. This integrative approach underscores the therapeutic potential of targeting the cGAS/STING pathway and provides a foundation for developing novel interventions aimed at alleviating inflammatory cardiomyopathy and improving patient outcomes. Future studies will be crucial in validating these findings and translating them into clinics.