The cGAS-STING Pathway: A Ubiquitous Checkpoint Perturbing Myocardial Attributes

Abstract

As an innate immune route of defense against microbial infringement, cyclic guanosine monophosphate (GMP)–adenosine monophosphate (AMP) synthase (cGAS)- stimulator of interferon genes (STING) signaling does not simply participate in amplifying inflammatory responses via releasing type-I interferon (IFN) or enhance the expression of pro-inflammatory genes, but also interplays with multifarious pathophysiological activities, such as autophagy, apoptosis, pyroptosis, ferroptosis, and senescence in a broad repertoire of cells like endothelial cells, macrophages and cardiomyocyte. Thus, the cGAS-STING pathway is closely linked with aberrant heart morphologically and functionally via these mechanisms. The past few decades have witnessed an increased interest in the exact relationship between the activation of the cGAS-STING pathway and the initiation or development of certain cardiovascular diseases (CVD). A group of scholars has gradually investigated the perturbation of myocardium affected by the overactivation or suppression of the cGAS-STING. This review focuses on how the cGAS-STING pathway interweaves with other pathways and creates a pattern of dysfunction associated with cardiac muscle. This sets treatments targeting the cGAS-STING pathway apart from traditional therapeutics for cardiomyopathy and achieves better clinical value.

The cGAS-STING pathway in cardiovascular diseases: from basic research to clinical perspectives

“…C-176 has become the most studied compound in cardiovascular research. Nitrofuran derivatives can palmitoylate Cys99 on STING proteins to alter their molecular properties and affect their response-mediated I-IFN transcription [ 123 ]. Hua et al[ 124 ] showed that in α-MyHC-induced autoimmune myocarditis (EAM), consecutive intraperitoneal injection of 1 μmol of C-176 for 14 days results in an inflammatory response in EAM, with IFN-β, TNF-α, CCL2, and F4/80 expression that is ameliorated by blocking macrophage STING expression.…”