CARD9 deficiency alleviates septic pulmonary embolism

Area of Science:

• Pulmonary Vascular Medicine
• Sepsis Pathophysiology
• Molecular Biology

Background:

• Dysfunction of pulmonary microvascular endothelial cells (PMVECs) is a critical factor in sepsis-associated pulmonary embolism (PE).
• Understanding the molecular mechanisms underlying PMVEC dysfunction in sepsis is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the role of caspase recruitment domain-containing protein 9 (CARD9) in sepsis-induced PE.
• To explore the therapeutic potential of Tiliroside (TIS) in modulating CARD9-mediated pathways.

Main Methods:

• Proteomic analysis of sepsis patient serum to identify differentially expressed proteins.
• Utilized wild-type (WT) and CARD9 knockout (KO) mice to model sepsis-induced PE.
• Established in vitro and in vivo sepsis models to assess PMVEC function.
• Evaluated the therapeutic effects of Tiliroside (TIS) on the CARD9-mediated MAPK/NF-κB pathway.

Main Results:

• Identified 46 differentially expressed proteins in pulmonary vascular endothelial tissues of mice with sepsis, including CARD9.
• CARD9 knockout and silencing ameliorated sepsis-induced PMVEC dysfunction in both in vivo and in vitro models.
• Tiliroside (TIS) significantly enhanced PMVEC function in sepsis by modulating the CARD9-mediated MAPK/NF-κB signaling pathway.

Conclusions:

• CARD9 is implicated in the pathogenesis of sepsis-induced PE by affecting PMVEC function.
• Targeting CARD9 presents a promising therapeutic avenue for sepsis-associated PE.
• Tiliroside demonstrates potential as a therapeutic agent for sepsis-induced PMVEC dysfunction via the CARD9 pathway.