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

Front Immunol. 2023 Dec 13:14:1287130. doi: 10.3389/fimmu.2023.1287130. eCollection 2023.

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.

Keywords: cGAS-STING; cardiovascular disease; dsDNA; inflammation; innate immune system.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiovascular Diseases*
  • DNA
  • Humans
  • Nucleic Acids*
  • Nucleotidyltransferases / metabolism
  • Signal Transduction / physiology

Substances

  • DNA
  • Nucleic Acids
  • Nucleotidyltransferases

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by National Natural Science Foundation of China (No. 82073852), Natural Science Foundation of Hubei Province (No. 2021CFB439, 2022CFB818), Hubei Province Department of Education (No. B2021228), National Research Project Cultivation Program of Hubei University of Science and Technology (No. 2020-22GP05), Hubei University of Science and Technology Innovation team project (No. 2022T01) and Hubei Key Laboratory of Diabetes and Angiopathy Team project (No. 2022TNB01).