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

Authors

Weiyue Wang
Yuanxu Gao
Hyun Kyoung Lee
Albert Cheung-Hoi Yu
Markus Kipp
Hannes Kaddatz
Jiangshan Zhan

Language

English

Publication Date

5-25-2025

Journal

Cells

DOI

10.3390/cells14110778

PMID

40497954

PMCID

PMC12153880

PubMedCentral® Posted Date

5-25-2025

PubMedCentral® Full Text Version

Post-print

Abstract

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.

Keywords

Humans, Nucleotidyltransferases, Membrane Proteins, Signal Transduction, Cardiomyopathies, Animals, Inflammation, cardiomyopathy, cGAS/STING pathway, mitochondria, DNA damage

Published Open-Access

yes

Recommended Citation

Wang, Weiyue; Gao, Yuanxu; Lee, Hyun Kyoung; et al., "The cGAS/STING Pathway: Friend or Foe in Regulating Cardiomyopathy" (2025). Duncan NRI Faculty and Staff Publications. 154.
https://digitalcommons.library.tmc.edu/duncar_nri_pub/154