CARD9 deficiency alleviates septic pulmonary embolism.

Abstract

Purpose: Dysfunction of pulmonary microvascular endothelial cells (PMVECs) is an important feature of pulmonary embolism (PE) in sepsis. This study aimed to explore the impact of caspase recruitment domain-containing protein 9 (CARD9) on sepsis-induced PE. Materials and Methods: Proteomic analysis was performed on serum of sepsis patients with PE to identify differentially expressed proteins. Wild-type (WT) and CARD9 knockout (KO) mice were used to establish PE in sepsis mouse model. In vitro and in vivo sepsis models were established to evaluate PMVEC function. Tiliroside (TIS) was tested for its therapeutic effects via modulation of the CARD9-mediated MAPK/NF-κB pathway. Results: In the pulmonary vascular endothelial tissues of mice with sepsis, a total of 46 proteins exhibited differential expression, and CARD9 was one of the changes proteins. Both CARD9 knockout (KO) and silencing were found to effectively ameliorate sepsis-induced dysfunction of PMVECs in both in vivo and in vitro models of sepsis. Tiliroside (TIS), an active constituent derived from Buddleja officinalis Maxim, demonstrated a significant capacity to enhance the function of PMVECs in sepsis by modulating the CARD9-mediated MAPK/NF-κB signaling pathway. Conclusion: In summary, CARD9 emerges as a potential molecular target for the treatment of sepsis-associated PE dysfunction.