A novel role of miR-223-3p in reducing NLRP3-mediated inflammation and deep vein thrombosis in a mouse model.

ObjectiveDeep vein thrombosis (DVT) is a global health issue caused by abnormal clotting in deep veins, which can lead to serious complications such as pulmonary embolism. This study is the first to validate the regulatory effect of miR-223-3p on the NLRP3 inflammasome in a mouse model of DVT, expanding its potential therapeutic value in venous thrombosis-associated inflammation.MethodsMicroRNA sequencing and quantitative real-time polymerase chain reaction (qRT-PCR) were conducted to assess miRNA expression in a DVT mouse model. The downstream target of miR-223-3p, NLRP3, was identified using miRNA target prediction databases and validated by qRT-PCR. Human umbilical vein endothelial cells (HUVECs) and a DVT mouse model were used to explore the functional relationship between miR-223-3p and Nlrp3.ResultsThe expression of miR-223-3p and Nlrp3 was significantly increased in the vein walls of mice with DVT. The tail vein injection of agomiR-223-3p reduced thrombus formation and downregulated the expression of Nlrp3, interleukin 6 (Il-6), interleukin 1 beta (IL-1beta) and Icam-1. In vitro, miR-223-3p overexpression reduced the expression of NLRP3, Il-6, IL-1beta and ICAM-1, whereas NLRP3 overexpression antagonized these effects. Additionally, miR-223-3p enhanced the viability and migration of LPS-stimulated HUVECs by reducing NLRP3 expression.ConclusionsOur findings suggest that miR-223-3p may play a role in alleviating inflammation and reducing the thrombus burden in mice with DVT by downregulating Nlrp3 expression, supporting its potential as a therapeutic target for DVT.