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

• Published in: Cells (Basel, Switzerland) Vol. 14; no. 11; p. 778
• Main Authors: Wang, Weiyue, Gao, Yuanxu, Lee, Hyun Kyoung, Yu, Albert Cheung-Hoi, Kipp, Markus, Kaddatz, Hannes, Zhan, Jiangshan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25.05.2025; MDPI
• Subjects: Animals; Apoptosis; Autophagy; B cells; Biological response modifiers; Cardiomyocytes; Cardiomyopathies - genetics; Cardiomyopathies - metabolism; Cardiomyopathies - pathology; Cardiomyopathy; Cardiovascular disease; Cell cycle; Cell death; Cellular stress response; cGAS/STING pathway; Coronary artery disease; Cyclic guanylic acid; Development and progression; Diabetes; DNA damage; DNA repair; Endoplasmic reticulum; Genes; Health aspects; Heart diseases; Heart failure; Humans; Immune response; Infection; Inflammation; Inflammation - metabolism; Interferon; Kinases; Literature reviews; Medical research; Medicine, Experimental; Membrane Proteins - metabolism; Metabolism; mitochondria; Mitochondrial DNA; Molecular modelling; Mutation; Nucleotidyltransferases - metabolism; Pathogenesis; Proteins; Review; RNA; RNA sequencing; Senescence; Signal Transduction; Therapeutic targets; cardiomyopathy; DNA damage; mitochondria; cGAS/STING pathway
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells14110778

Inflammation is a central hallmark of cardiomyopathy, where misdirected immune responses contribute to chronic myocardial dysfunction. Among the emerging molecular mechanisms implicated in this process, the cyclic GMP–AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway has garnered increasing attention. Acting as a key cytosolic DNA sensor, the cGAS/STING pathway orchestrates inflammatory responses triggered by microbial infections or endogenous cellular stressors such as autophagy and apoptosis. Despite its pivotal role, the precise molecular mechanisms regulating this pathway and its role in cardiomyopathy-associated inflammation remain poorly understood and subject to ongoing debate. To address this scientific gap, we first reviewed key findings on cGAS/STING signaling in various forms of cardiomyopathy, drawing from in vivo and in vitro studies, as well as clinical samples. In the next step, we explored how the cGAS/STING pathway could be modulated by specific agonists and antagonists in the context of cardiac disease. Finally, by integrating publicly available human single-cell RNA sequencing (scRNA-seq) data and a systematic literature review, we identified existing molecular interventions and highlighted promising therapeutic targets aimed at mitigating cGAS/STING-driven inflammation. This comprehensive approach emphasizes 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 essential to validate these findings and facilitate their translation into clinical practice.