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

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.