CARD9 Regulation and its Role in Cardiovascular Diseases

Int J Biol Sci. 2022 Jan 1;18(3):970-982. doi: 10.7150/ijbs.65979. eCollection 2022.

Abstract

Caspase recruitment domain-containing protein 9 (CARD9) is an adaptor protein expressed on myeloid cells and located downstream of pattern recognition receptors (PRRs), which transduces signals involved in innate immunity. CARD9 deficiency is associated with increased susceptibility to various fungal diseases. Increasing evidence shows that CARD9 mediates the activation of p38 MAPK, NF-κB, and NLRP3 inflammasome in various CVDs and then promotes the production of proinflammatory cytokines and chemokines, which contribute to cardiac remodeling and cardiac dysfunction in certain cardiovascular diseases (CVDs). Moreover, CARD9-mediated anti-apoptosis and autophagy are implicated in the progression of CVDs. Here, we summarize the structure and function of CARD9 in innate immunity and its various roles in inflammation, apoptosis, and autophagy in the pathogenesis of CVDs. Furthermore, we discuss the potential therapies targeting CARD9 to prevent CVDs and raise some issues for further exploring the role of CARD9 in CVDs.

Keywords: CARD9; apoptosis; autophagy; cardiovascular diseases; inflammation; innate immunity.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • CARD Signaling Adaptor Proteins / genetics
  • CARD Signaling Adaptor Proteins / metabolism
  • Candidiasis, Chronic Mucocutaneous*
  • Cardiovascular Diseases* / genetics
  • Cytokines / metabolism
  • Humans
  • Immunity, Innate

Substances

  • Adaptor Proteins, Signal Transducing
  • CARD Signaling Adaptor Proteins
  • CARD9 protein, human
  • Cytokines