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Identification of thrombomodulin as a dynamic monitoring biomarker for deep venous thrombosis evolution
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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791923/ https://www.ncbi.nlm.nih.gov/pubmed/33456509 http://dx.doi.org/10.3892/etm.2020.9574 |
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author | Cheng, Xi Sun, Baolan Liu, Shiyi Li, Dandan Yang, Xiaoqing Zhang, Yuquan |
author_facet | Cheng, Xi Sun, Baolan Liu, Shiyi Li, Dandan Yang, Xiaoqing Zhang, Yuquan |
author_sort | Cheng, Xi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7791923 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-77919232021-01-14 Identification of thrombomodulin as a dynamic monitoring biomarker for deep venous thrombosis evolution Cheng, Xi Sun, Baolan Liu, Shiyi Li, Dandan Yang, Xiaoqing Zhang, Yuquan Exp Ther Med Articles 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. D.A. Spandidos 2021-02 2020-12-14 /pmc/articles/PMC7791923/ /pubmed/33456509 http://dx.doi.org/10.3892/etm.2020.9574 Text en Copyright: © Cheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Cheng, Xi Sun, Baolan Liu, Shiyi Li, Dandan Yang, Xiaoqing Zhang, Yuquan Identification of thrombomodulin as a dynamic monitoring biomarker for deep venous thrombosis evolution |
title | Identification of thrombomodulin as a dynamic monitoring biomarker for deep venous thrombosis evolution |
title_full | Identification of thrombomodulin as a dynamic monitoring biomarker for deep venous thrombosis evolution |
title_fullStr | Identification of thrombomodulin as a dynamic monitoring biomarker for deep venous thrombosis evolution |
title_full_unstemmed | Identification of thrombomodulin as a dynamic monitoring biomarker for deep venous thrombosis evolution |
title_short | Identification of thrombomodulin as a dynamic monitoring biomarker for deep venous thrombosis evolution |
title_sort | identification of thrombomodulin as a dynamic monitoring biomarker for deep venous thrombosis evolution |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791923/ https://www.ncbi.nlm.nih.gov/pubmed/33456509 http://dx.doi.org/10.3892/etm.2020.9574 |
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