Abstract: BACKGROUND: Vascular endothelial cell dysfunction is the core factor in the pathogenesis of preeclampsia. Lipopolysaccharide can be used to establish a rat model of preeclampsia, but the effect and mechanism on endothelial cells have not been fully clarified.
OBJECTIVE: To investigate the effect of lipopolysaccharides on the function of human umbilical vein endothelial cells and its possible mechanism.
METHODS: Human umbilical vein endothelial cells were divided into control group and lipopolysaccharides group. The functional changes of human umbilical vein endothelial cells after lipopolysaccharides treatment in both groups were detected by the following experiments: Cell adhesion test was used to detect the adhesion of monocytes to human umbilical vein endothelial cells. Tubule formation experiment was used to detect the tubule formation ability of human umbilical vein endothelial cells. The mRNA expression levels of nucleotide binding oligomerization domain-like receptor protein 3, interleukin-1β, 6-phosphofructo-2-kinase and endothelial nitric oxide synthase were detected by qPCR. Western blot assay was utilized to detect the protein expression levels of nucleotide binding oligomerization domain-like receptor protein 3, 6-phosphofructo-2-kinase 3, intercellular adhesion molecule 1, and endothelial nitric oxide synthase. Human umbilical vein endothelial cells were divided into control group, lipopolysaccharide group, and MCC950 (nucleotide binding oligomerization domain-like receptor protein 3 inhibitor) group. qPCR was used to detect the mRNA expression levels of nucleotide binding oligomerization domain-like receptor protein 3, interleukin-1β, 6-phosphofructo-2-kinase 3 and endothelial nitric oxide synthase.
RESULTS AND CONCLUSION: (1) Compared with the control group, the expression of intercellular adhesion molecule-1 protein in lipopolysaccharides group increased (P < 0.05), and the adhesion of monocytes increased (P < 0.05), suggesting that human umbilical vein endothelial cells were activated and their adhesion ability was enhanced. (2) Compared with the control group, the tubule formation ability of human umbilical vein endothelial cells was inhibited in the lipopolysaccharides group (P < 0.05). (3) Compared with the control group, the mRNA and protein expression levels of endothelial nitric oxide synthase were decreased in the lipopolysaccharides group (P < 0.05); mRNA expression levels of nucleotide binding oligomerization domain-like receptor protein 3, interleukin-1β, and 6-phosphofructo-2-kinase, as well as the protein expression levels of nucleotide binding oligomerization domain-like receptor protein 3 and 6-phosphofructo-2-kinase 3 were increased (P < 0.05). (4) Compared with the lipopolysaccharides group, the mRNA expressions of interleukin-1β and 6-phosphofructo-2-kinase 3 were decreased, and the mRNA expression of endothelial nitric oxide synthase was increased in the MCC950 group (P < 0.05). The results suggest that lipopolysaccharides can cause dysfunction of human umbilical vein endothelial cells, which may be regulated by the nucleotide-binding oligomerization domain-like receptor protein 3/interleukin-1β/6-phosphofructo-2-kinase 3 pathway. 

Key words: lipopolysaccharides, endothelial cell, nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), interleukin-1β, 6-phosphofructo-2-kinase 3 (PFKFB3), preeclampsia