Link between sterile inflammation and cardiovascular diseases: Focus on cGAS-STING pathway in the pathogenesis and therapeutic prospect

Abstract

Sterile inflammation characterized by unresolved chronic inflammation is well established to promote the progression of multiple autoimmune diseases, metabolic disorders, neurodegenerative diseases, and cardiovascular diseases, collectively termed as sterile inflammatory diseases. In recent years, substantial evidence has revealed that the inflammatory response is closely related to cardiovascular diseases. Cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway which is activated by cytoplasmic DNA promotes the activation of interferon regulatory factor 3 (IRF3) or nuclear factor-κB (NF-κB), thus leading to upregulation of the levels of inflammatory factors and interferons (IFNs). Therefore, studying the role of inflammation caused by cGAS-STING pathway in cardiovascular diseases could provide a new therapeutic target for cardiovascular diseases. This review focuses on that cGAS-STING-mediated inflammatory response in the progression of cardiovascular diseases and the prospects of cGAS or STING inhibitors for treatment of cardiovascular diseases.

Does cardiac impairment develop in ischemic renal surgery in rats depending on the reperfusion time?

“…Sterile inflammation involved in the development of heart failure can triggered by mtDNA [ 48 ]. According to previous studies, this sterile inflammatory response contributes to cardiac dysfunction by promoting leukocyte infiltration, cytokine release, and oxidative stress [ 49 , 50 ]. Furthermore, mitochondrial ROS production during renal IR injury can directly damage cardiomyocytes by inducing oxidative stress and impairing mitochondrial function [ 51 ].…”

Molecular map of cGAS-STING pathway-related genes in bladder cancer: the perspective toward immune microenvironment and prognosis

“…The cGAS-STING pathway, triggered by DNA present in the cytoplasm, facilitates the activation of two key transcription factors, namely interferon regulatory factor 3 (IRF3) and nuclear factor-κB (NF-κB). This activation subsequently results in the elevation of inflammatory factors and interferons (IFNs) [ 26 ]. IKKβ/IKBKB, referred to as IκB kinase beta or IKK2, acquired its nomenclature due to its role in the phosphorylation of IκB molecules, which function as inhibitors of NF-κB transcription factors [ 27 ].…”

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

“…Aseptic inflammation is the absence of microbial infection and features of intractable chronic inflammation that promote the development of autoimmune, metabolic, neurodegenerative, and cardiovascular diseases [ 86 ]. Inflammation requires either exogenous (e.g., microorganisms, bacteria, and viruses) or endogenous (e.g., autologous DNA, proteins, and lipids) ligands that activate downstream inflammatory signals [ 87 ].…”