Trafficking and effect of released DNA on cGAS-STING signaling pathway and cardiovascular disease

Abstract

Evidence from clinical research and animal studies indicates that inflammation is an important factor in the occurrence and development of cardiovascular disease (CVD). Emerging evidence shows that nucleic acids serve as crucial pathogen-associated molecular patterns (PAMPs) or non-infectious damage-associated molecular patterns (DAMPs), are released and then recognized by pattern recognition receptors (PRRs), which activates immunological signaling pathways for host defense. Mechanistically, the released nucleic acids activate cyclic GMP-AMP synthase (cGAS) and its downstream receptor stimulator of interferon genes (STING) to promote type I interferons (IFNs) production, which play an important regulatory function during the initiation of an innate immune response to various diseases, including CVD. This pathway represents an essential defense regulatory mechanism in an organism’s innate immune system. In this review, we outline the overall profile of cGAS-STING signaling, summarize the latest findings on nucleic acid release and trafficking, and discuss their potential role in CVD. This review also sheds light on potential directions for future investigations on CVD.

Recent advances of myotubularin-related (MTMR) protein family in cardiovascular diseases

“…Though MTMR4 may affect aortic aneurysm via affecting TGFβ signaling pathway, there is no direct evidence that MTMR4 has definite curable effects on aortic aneurysm. In addition, Dy et al (2019) found that MTMR3/MTMR4 regulated interferon gene stimulating factor (STING) trafficking by regulating ptdins3p production, suggesting that MTMR3/MTMR4 may be a potential therapeutic target in the process of myocardial fibrosis, macrophage infiltration and cardiac inflammatory response in patients with diabetes and obesity mediated by STING signaling, which needs to be further experimentally verified ( 43 ).…”

“…In spite of the effect on promoting late autophagy, MTMR6 also exerts as an antagonism under stress via interference with PI3K signal pathway and inhibiting formation of autophagosome ( 4 ). There have also been reports that deletion of either the MTMR6 or the MTMR8/MTMR9 complex leads to an increase in autophagy ( 43 , 91 ). Wang et al found that negative regulation of MTMR6 can inhibit the proliferation of ovarian cancer cells and promote apoptosis.…”