Study on the Mechanism of NLRP3/IL-1/ NF-κB Signaling Pathway and Macrophage Polarization in the Occurrence and Development of VTE

Abstract

The role of inflammation in venous thromboembolism (VTE) has been the focus of recent research. The NLRP3/IL-1/NF-κB signaling pathway and cytokines such as IL-1, regulated by macrophage polarization, may be the key indicators of a prethrombotic state; however, the mechanisms by which they affect the occurrence of VTE remain unclear. We used neurobiological clamps to stimulate the vein wall to induce vascular endothelial damage to generate a rat model of VTE, applied enzyme-linked immunosorbent assay and real time-polymerase chain reaction technology to identify key proteins (IL1β, Caspase-1, NLRP3, and NF-κB P65), gene mRNA levels and protein expression levels of the NLRP3/IL-1/NF-κB signaling pathway in each group of Sprague Dawley rats, and observed the polarization state of M1 (CD86) and M2 (CD206) macrophages using immunohistochemistry. A dark red, small thrombus developed in the inferior vena cava immediately after modeling in the model and inhibitor groups. The plasma levels of IL-1 and TNF-α, mRNA expression of key proteins (IL1β, Caspase-1, NLRP3, and NF-κB P65), and expression of key proteins (IL1β, Caspase-1, NLRP3, and NF-κB P65) in VTE model rats were significantly higher than inhibitor, sham operation, and normal control groups (P<0.05). Six hours after VTE modeling, M1 type macrophages were more significantly increased than M2 type macrophages in thrombus tissue (P<0.05). Our analyses demonstrated that the nod-like receptor protein3/Interleukin-1/nuclear factor-κB signaling pathway and macrophage polarization are important in the occurrence and development of VTE and that their target regulation may become a new strategy for VTE prevention and treatment.