Department of Cardiovascular Diseases, First Hospital of Jilin University, Jilin University, Changchun, 130021, China.
Pediatric Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY, 40202, USA.
Int J Biol Sci. 2022 Jan 1;18(3):970-982. doi: 10.7150/ijbs.65979. eCollection 2022.
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.
衔接蛋白包含半胱氨酸天冬氨酸酶募集域蛋白 9(CARD9)是一种在髓样细胞中表达的衔接蛋白,位于模式识别受体(PRRs)的下游,其传递参与固有免疫的信号。CARD9 缺陷与各种真菌感染病的易感性增加有关。越来越多的证据表明,CARD9 在各种心血管疾病(CVDs)中介导 p38 MAPK、NF-κB 和 NLRP3 炎性小体的激活,进而促进促炎细胞因子和趋化因子的产生,导致某些心血管疾病中的心脏重构和心功能障碍。此外,CARD9 介导的抗细胞凋亡和自噬参与了 CVD 的进展。在这里,我们总结了 CARD9 在先天免疫中的结构和功能,以及其在 CVD 发病机制中的炎症、凋亡和自噬中的各种作用。此外,我们讨论了针对 CARD9 的潜在治疗方法,以预防 CVD,并提出了一些问题,以进一步探讨 CARD9 在 CVD 中的作用。