CARD9 Regulation and its Role in Cardiovascular Diseases

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.

CARD9 Signaling, Inflammation, and Diseases

“…It has been well established that excessive inflammation, ROS production and related oxidative stress significantly contribute to CVDs, including atherosclerosis, cardiac fibrosis, coronary artery disease, myocardial infarction, and heart failure ( 4 , 6 , 86 , 149 ). CARD9-mediated signaling in CVDs has been well documented in several reviews ( 4 , 16 , 150 ). Briefly, CARD9-mediated production of cytokines and chemokines results in cardiovascular dysfunction by instigating a positive feedback loop of inflammation and oxidative stress.…”