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CC BY 4.0 · TH Open 2022; 06(03): e194-e212
DOI: 10.1055/a-1801-2055
Review Article

Circulating Thrombomodulin: Release Mechanisms, Measurements, and Levels in Diseases and Medical Procedures

Mallorie Boron
1   Department of Chemistry and Chemical and Biomedical Engineering and Center for Gene Regulation in Health and Disease (GRHD), Cleveland State University, Cleveland, Ohio, United States
,
Tiffany Hauzer-Martin
1   Department of Chemistry and Chemical and Biomedical Engineering and Center for Gene Regulation in Health and Disease (GRHD), Cleveland State University, Cleveland, Ohio, United States
,
Joseph Keil
1   Department of Chemistry and Chemical and Biomedical Engineering and Center for Gene Regulation in Health and Disease (GRHD), Cleveland State University, Cleveland, Ohio, United States
,
Xue-Long Sun 
1   Department of Chemistry and Chemical and Biomedical Engineering and Center for Gene Regulation in Health and Disease (GRHD), Cleveland State University, Cleveland, Ohio, United States
› Author Affiliations Sources of Funding X.-L.S.is supported by research grant from the U.S. National Heart, Lung, and Blood Institute of the National Institutes of Health under award no. 1R15HL138544–01.
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Abstract

Thrombomodulin (TM) is a type-I transmembrane protein that is mainly expressed on endothelial cells and plays important roles in many biological processes. Circulating TM of different forms are also present in biofluids, such as blood and urine. Soluble TM (sTM), comprised of several domains of TM, is the major circulating TM which is generated by either enzymatic or chemical cleavage of the intact protein under different conditions. Under normal conditions, sTM is present in low concentrations (<10 ng/mL) in the blood but is elevated in several pathological conditions associated with endothelial dysfunction such as cardiovascular, inflammatory, infection, and metabolic diseases. Therefore, sTM level has been examined for monitoring disease development, such as disseminated intravascular coagulation (DIC), sepsis and multiple organ dysfunction syndrome in patients with novel coronavirus disease 2019 (COVID-19) recently. In addition, microvesicles (MVs) that contain membrane TM (MV-TM) have been found to be released from activated cells which also contribute to levels of circulating TM in certain diseases. Several release mechanisms of sTM and MV-TM have been reported, including enzymatic, chemical, and TM mutation mechanisms. Measurements of sTM and MV-TM have been developed and explored as biomarkers in many diseases. In this review, we summarize all these advances in three categories as follows: (1) release mechanisms of circulating TM, (2) methods for measuring circulating TM in biological samples, and (3) correlation of circulating TM with diseases. Altogether, it provides a whole picture of recent advances on circulating TM in health and disease.

Keywords

circulating thrombomodulin - COVID-19 - endothelial cell - microvesicle - sepsis - soluble thrombomodulin - thrombomodulin - vascular damage

Author Contribution

M.B., T.H.-M., and X.-L.S. prepared the first draft; all authors contributed to the concept, literature search, conclusions, and editing of the final version.


Supplementary Material



Publication History

Received: 29 October 2021

Accepted: 11 March 2022

Accepted Manuscript online:
17 March 2022

Article published online:
11 July 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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