Human Atheromatous Plaques Expressed Sensing Adaptor STING, a Potential Role in Vascular Inflammation Pathogenesis

Introduction

Atherogenesis is a complex physiological process that involves inflammation, and it is a significant contributor to plaque development and plaque vulnerability. Immune activation can be behind the increased inflammation in atherosclerosis.[1] In many organisms, detecting foreign DNA is an essential part of immunity. The cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway has emerged as an effective mechanism for connecting DNA sensing to the production of potent innate immune defense programs and it plays a substantial role in this process in mammalian cells.[2] The allosteric activation of cGAS' catalytic activity by binding to double-stranded DNA leads to the formation of 2′,3′-cyclic GMP–AMP (cGAMP), a second messenger molecule and potent agonist of STING. The activation of the cGAS–STING pathway is triggered by a fundamental constituent of life (particularly DNA), and it lacks any pathogen-specific characteristics, which distinguishes it from several other innate immune signaling mechanisms. As a result, cGAS identifies a wide range of DNA species, both foreign and self-derived.

Even though pathological process inducers are disease-specific, there is evidence for the cGAS–STING pathway's role as a driver of both (hyper-)acute and chronic, low-grade inflammatory states associated with a variety of illnesses.[3] This role is not unexpected due to its fundamental function as a ubiquitous and sensitive mechanism for out-of-context DNA recognition. Furthermore, preliminary evidence suggested that intracellular trafficking pathway abnormalities can significantly impact STING activity, and it contributes to inappropriate immune activation. Although chronic low-grade inflammatory stages have been associated with atherosclerosis, the cGAS–STING pathway has not been explored in this relevant pathophysiological process. Here, we explored the expression of STING protein in the artheriosclerotic (ATC) plaque of human patients who underwent carotid endarterectomy.

Author Contributions

F.P., N.T., and M.P-.O. conceived the study. G.A. and J.P. designed the experiments. N.T., J.P., G.A.: sample processing, data analysis, and data interpretation. G.A., F.P., and M.P-.O.: drafted the manuscript. M.P.O. and F.P. procured funding. All authors critically revised and approved the final version of the manuscript.

^* These authors contributed equally to this work.

^** These authors contributed equally to this work as senior authors.

Publikationsverlauf

Eingereicht: 20. September 2021

Angenommen: 12. Februar 2022

Accepted Manuscript online:
15. Februar 2022

Artikel online veröffentlicht:
05. Mai 2022

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