Inhibition of LOX-1 ameliorates coagulation and inflammation in sepsis by suppressing the JAK2/STAT3 pathway

Lectin-like oxidised low-density lipoprotein receptor-1 (LOX-1) is a transmembrane protein that belongs to the C-type lectin family and plays a significant role in various diseases by promoting the release of inflammatory mediators and enhancing cellular responses to oxidative stress. Studies have demonstrated that in sepsis, activation of LOX-1 promotes a procoagulant phenotype in endothelial cells. The aim of this study was to investigate whether inhibition of LOX-1 could ameliorate coagulation dysfunction and the inflammatory response in sepsis by modulating the JAK2/STAT3 signaling pathway. We utilized LPS-induced C57BL/6 mice to establish an in vivo animal model and assessed the activity of the JAK2/STAT3 signaling pathway, along with coagulation-related factors and inflammatory factors.In the in vitro experiments, human umbilical vein endothelial cells (HUVECs) were exposed to LPS after either LOX-1 knockdown or no treatment. We subsequently measured the expression of tissue factor (TF) and inflammatory factors, as well as changes in the JAK2/STAT3 signaling pathway. The results indicated that LOX-1 blockade improved coagulation dysfunction and the inflammatory response, leading to enhanced survival in septic mice. In vitro, LOX-1 knockdown suppressed the expression of TF and inflammatory factors in LPS-induced HUVECs. Both in vivo and in vitro experiments confirmed that inhibition of LOX-1 ameliorated sepsis by suppressing the JAK2/STAT3 signaling pathway.