cGAS-STING targeting offers a novel therapeutic paradigm in cardiovascular diseases
Yu Wang, Weixue Wang, Yi Zhang, Pu Gao, Joshua S. Fleishman, Hongquan Wang
Abstract
Cyclic GMP/AMP (cGAMP) synthase (cGAS), along with the endoplasmic reticulum (ER)-associated stimulator of interferon genes (STING), are crucial elements of the type 1 interferon response. cGAS senses microbial DNA and self-DNA, labeling cGAS-STING as a crucial mechanism in autoimmunity, sterile inflammatory responses, and cellular senescence. However, chronic and aberrant activation of the cGAS/STING axis results in inflammatory and autoimmune diseases. cGAS-STING has emerged as a vital mechanism driving inflammation-related diseases, including cardiovascular diseases (CVDs). Insights into the biology of the cGAS-STING pathway have enabled the discovery of small-molecule agents which have the potential to inhibit the cGAS-STING axis in many human diseases. In this review, we first outline the principal components of the cGAS-STING signaling cascade. From such we discuss recent research that highlights general mechanisms by which cGAS-STING contributes to CVDs. Then, we summarize a list of bioactive small-molecule compounds which modulate the cGAS-STING axis, reviewing their potential clinical applications. Finally, we discuss key limitations of this new proposed therapeutic approach and provide possible techniques to overcome them.These review highlights a novel groundbreaking therapeutic possibilities through targeting cGAS-STING in CVDs.