The present study aimed to investigate the effect of the expression of interleukin (IL)-18 and related markers on deep venous thrombosis (DVT) to examine their correlation. Sprague-Dawley rats of different models were established and were randomly assigned into three groups. The expression of IL-18, nuclear factor (NF)-κB and von Willebrand factor (vWF) were detected in blood samples. The inferior vena cava (IVC) was ligated to establish the DVT model. Rat IL-18 overexpression and inhibition vectors were constructed. The expression levels of IL-18 and related markers in the venous wall were compared between the model group and the control group using reverse transcription-quantitative polymerase chain reaction and western blot analyses. Following the culture of human umbilical vein endothelial cells (HUVECs), IL-18 was added to the cells, following which the growth of the HUVECs, and changes in vWF and other endothelial functional markers were analyzed. The IVC model demonstrated complete thrombosis at 8 h and stable thrombosis at 24 h. At 24 h following model establishment, the expression levels of IL-18, NF-κB and vWF were high in the blood samples with the occurrence and development of thrombosis (P<0.05). The weight, length and weight/length ratio of thrombi in each model group showed significant differences from those in the control group (P<0.05) with the overexpression of IL-18, and the expression levels of NF-κB and vWF in venous tissues were altered with abnormal expression levels of IL-18. IL-18 damaged HUVECs and significantly increased viability in early-stage apoptosis, promoted the upregulation of vWF and P-selectin, and reduced tissue plasminogen activator. IL-18 and the related markers were closely associated with the occurrence and development of DVT.

Krüppel-like family (KLF) members are important regulators of proinflammatory activation in the vasculature. A transcriptome study involving RNA sequencing (RNA-seq) and quantitative PCR (qPCR) was performed to investigate Klf15 and Klf15-regulated gene levels in C57BL/6 mice with inferior vena cava thrombi and in control (Blank) mice. A total of 2,206 differentially expressed genes (DEGs), including 1,330 upregulated and 876 downregulated genes, were identified between the deep venous thrombosis (DVT) group and the Blank group. Additionally, 1,041 DEGs (235 upregulated and 806 downregulated) were identified between the Klf15-small interfering RNA (siRNA) and Klf15-negative control (NC) groups. The DEGs were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, and qPCR was conducted to validate the results. A total of seven significant DEGs were selected from the RNA-seq results. Matrix metalloproteinases (Mmp)12, Mmp13, Mmp19, Arg1, Ccl2, heme oxygenase-1 and Fmo3 levels were significantly higher, while Klf15 levels were lower, in the DVT group than in the Blank group. Fmo3 and Mmp19 have not been previously identified as DVT-associated DEGs. Klf15, Mmp12 and Mmp13 levels were compared between the Klf15-siRNA and Klf15-NC groups. Mmp12 and Mmp13 expression was significantly higher, while that of Klf15 was lower, in the Klf15-siRNA group than in the Klf15-NC group. Critical roles of Klf15, Mmp12 and Mmp13 have been identified, which have not previously been shown to help regulate DVT initiation and progression. Moreover, Klf15-mediated regulation of DVT may be modulated by downregulation of various genes, such as Mmp12 and Mmp13, potentially providing a theoretical foundation and diagnostic criteria for DVT treatment.

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