Identification of thrombomodulin as a dynamic monitoring biomarker for deep venous thrombosis evolution

Abstract

It has been demonstrated that thrombomodulin (TM) serves an important role in the formation of deep venous thrombosis (DVT) and is regarded to be a marker that can be used to measure vascular endothelial cell damage. However, how TM levels change during DVT evolution has not yet been well understood. The current study aimed to investigate the dynamic changes of TM during the evolution of DVT and explore the possible mechanisms behind these. A total of 48 patients newly diagnosed with DVT and 23 matched healthy controls were enrolled in the present study, and their plasma TM levels were examined and compared. In addition, a DVT model was established using Sprague-Dawley rats via the 'stenosis' method. The thrombi size, histopathologic changes and expression of TM and NF-κB in plasma and venous endothelium were measured at 9 different time points (1, 4, 6, 12 and 24 h, and at 3, 7, 14 and 21 days). Finally, the effect of inhibiting the activation of NF-κB on TM was investigated using pyrrolidine dithiocarbamate (PDTC), which is a potent inhibitor of the NF-κB pathway. The results of the current study indicated that the mean level of plasma TM in patients with DVT was significantly increased compared with healthy controls. In addition, thrombi size (clot length and weight), TM and NF-κB expression in the animal model plasma exhibited three distinct periods (1-12, 24 h-day 7 and 14-21) of markedly different results between periods. Immunofluorescence results confirmed the co-localization of TM and NF-κB in endothelial cells. In addition, it was indicated that the expression of TM in the endothelium of DVT models was upregulated compared with the control, while NF-κB was significantly downregulated. Following the administration of PDTC, the level of NF-κB and TM in the plasma were decreased significantly dose-dependently. The results of the current study suggested that TM was involved in the evolution of DVT and may be used as a dynamic biomarker to measure disease activity. Furthermore, the expression of TM during the evolution of DVT was indicated to be associated with the NF-κB signaling pathway.

The mechanism by which enoxaparin sodium–high-viscosity bone cement reduces thrombosis by regulating CD40 expression in endothelial cells

“…In this study, vascular tissues in contact with bone cement were selected to compare the influence of ES-PMMA and PMMA on the expression of thrombosis-related proteins in vascular endothelial cells and to illustrate the difference in the influence of these two types of bone cement on thrombosis by measuring the expression of these proteins. Among the many proteins expressed by endothelial cells, endothelin [ 15 ], vascular endothelial cell adhesion molecule [ 16 ], CD62p [ 17 , 18 ], CD31 [ 19 ], thermoregulatory protein [ 20 , 21 ], and CD40 [ 22 , 23 ] are closely related to thrombosis. We assessed the differential expression of thrombus-related proteins in endothelial cells by RT–qPCR and Western blotting and found that the expression of CD40 in the M group was significantly lower than that in the Con group.…”

Mechanism of novel enoxaparin sodium high viscosity bone cement reducing thrombosis by regulating the expression of CD40 in endothelial cells

“…The cause of local thrombosis caused by high viscosity bone cement is that bone cement directly contacts with blood components or acts on vascular endothelial tissue. In this study, the vascular tissues in contact with bone cement were selected to compare the in uence of new high-viscosity bone cement and ordinary highviscosity bone cement on the expression of thrombosis related proteins in vascular endothelial cells, and to illustrate the difference of the in uence of these two high-viscosity bone cements on thrombosis by measuring the expression of these proteins.Among many proteins expressed by endothelial cells, endothelin [34,35], vascular endothelial cell adhesion molecule [36,37], CD62p [38,39], CD31 [40,41], thromboregulatory protein [42][43][44], and CD40 [45][46][47] are closely related to thrombosis. We detected the differential expression of endothelial cells and thrombus related proteins by RT-qPCR and WesternBlot, and found that the expression of CD40 in M group was signi cantly lower than that in Con group, which was statistically signi cant.…”

Effect of thrombomodulin gene polymorphisms on venous thromboembolism: An analysis of evidence involving 6,629 patients

“…The expression of TM can reflect the progression of DVT and has a good prognostic effect. 39 Studies have revealed that TM has good sensitivity and specificity in the diagnosis of DVT in Asian populations. 40 THBD c1418 C>T polymorphisms was not associated with the risk of PE, which may be due to the lack of included studies.…”