Serum thrombomodulin

Boehme, M. W. J.; Nawroth, Peter P.; Kling, Elisabeth; Lin, Jie; Amiral, Jean; Riedesel, J.; Raeth, U.; Scherbaum, W. A.

doi:10.1002/art.1780370419

Cited by 45 publications

(7 citation statements)

References 14 publications

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“…Neutrophils and monocytes adherent to the endothelium can interact with activated platelets through the selectins expressed on its surface [133,134]. Activated monocytes release cytokines that down-regulate TM and EPCR synthesis (108,(135)(136)(137), and TM may be inactivated by oxidation of a methionine in the epidermal growth factor-like domain [138] or degradation by elastase released from activated neutrophils [139] (Figure 4). Vesiculated, activated platelets can then propagate coagulation very efficiently [140,141].…”

Section: Inflammation and Coagulationmentioning

confidence: 98%

The Multifunctional Protein C System

España¹,

Medina²,

Navarro³

et al. 2005

CMCCHA

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The protein C pathway is a major regulator of blood coagulation, since it controls the conversion of prothrombin to thrombin through a feedback inhibition mechanism. Protein C circulates in plasma as an inactive zymogen and is activated on the surface of endothelial cells by the thrombin-thrombomodulin complex, a process that can be further enhanced when protein C binds to its membrane receptor, the endothelial-cell protein C receptor. Activated protein C (APC) is then released from the complex, binds protein S and inhibits thrombin formation by inactivating coagulation factors Va and VIIIa. The importance of the protein C anticoagulant pathway is emphasized by the increased risk of venous thromboembolism (VTE) associated with protein C and protein S deficiencies, the factor V Leiden mutation, and reduced circulating APC levels. The protein C pathway also plays a significant role in inflammatory processes, since it prevents the lethal effects of E. coli-associated sepsis in animal models and improves the outcome of patients with severe sepsis. APC seems to display anti-apoptotic and neuroprotective activities. Thus, it reduces organ damage in animal models of sepsis, ischemic injury, endothelial cell injury, or stroke. Further research will hopefully widen the current therapeutic perspectives in all these illnesses, where these effects might play a crucial role in their treatment. This review will summarize the mechanisms that contribute to these biological activities of the protein C pathway.

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Section: Inflammation and Coagulationmentioning

confidence: 98%

The Multifunctional Protein C System

España¹,

Medina²,

Navarro³

et al. 2005

CMCCHA

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“…145 Markers for endothelial cell injury, like sTM, could be useful for helping determine the diagnosis or severity of the disease. 146 147 sTM levels as a whole are elevated in patients, both adults and juveniles, suffering from SLE. 95 148 TM levels also showed a positive correlation with disease activity and was stronger versus other markers such as E-selectin and sICAM-1.…”

Section: Introductionmentioning

confidence: 96%

“…95 148 TM levels also showed a positive correlation with disease activity and was stronger versus other markers such as E-selectin and sICAM-1. 146 148 149 150 151 Complications of SLE related with increasing sTM levels include nephritis, vasculitis, and central nervous system (CNS) lupus. 146 152 sTM levels were also useful in distinguishing between patients with active lupus nephritis (LN) or inactive LN.…”

Section: Introductionmentioning

confidence: 99%

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

Boron

Hauzer-Martin

Keil

et al. 2022

TH Open

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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 coronavirus disease-2019 (COVID-19) recently. In addition, microvesicles that contain membrane TM (microvesicle-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 microvesicle-TM have been reported, including enzymatic, chemical and TM mutation mechanisms. Measurements of sTM and microvesicle-TM have been developed and explored as biomarkers in many diseases. In this review, we summarize all these advances in three categories: (i) release mechanisms of circulating TM, (ii) methods for measuring circulating TM in biological samples, and (iii) correlation of circulating TM with diseases. Altogether, it provides a whole picture of recent advances on circulating TM in health and disease.

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“…TM has been described as an anti-inflammatory agent in the reduction of acute kidney injury and experimental glomerulonephritis ( Ikeguchi et al 2002 , Rajashekhar et al 2012 ). Additionally, diseases presenting endothelial injury including sepsis, severe malaria and dengue haemorrhagic fever display noticeable elevation of soluble TM ( Boehme et al 1994 , Ohnishi 1999 , Page & Liles 2013 ).…”

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confidence: 99%

The involvement of endothelial mediators in leprosy

Costa

Latini

Nogueira

2016

Mem. Inst. Oswaldo Cruz

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Leprosy is a chronic infectious disease that requires better understanding since it continues to be a significant health problem in many parts of the world. Leprosy reactions are acute inflammatory episodes regarded as the central etiology of nerve damage in the disease. The activation of endothelium is a relevant phenomenon to be investigated in leprosy reactions. The present study evaluated the expression of endothelial factors in skin lesions and serum samples of leprosy patients. Immunohistochemical analysis of skin samples and serum measurements of VCAM-1, VEGF, tissue factor and thrombomodulin were performed in 77 leprosy patients and 12 controls. We observed significant increase of VCAM-1 circulating levels in non-reactional leprosy (p = 0.0009). The immunostaining of VEGF and tissue factor was higher in endothelium of non-reactional leprosy (p = 0.02 for both) than healthy controls. Patients with type 1 reaction presented increased thrombomodulin serum levels, compared with non-reactional leprosy (p = 0.02). In type 2 reaction, no significant modifications were observed for the endothelial factors investigated. The anti-inflammatory and antimicrobial activities of the endotfhelial factors may play key-roles in the pathogenesis of leprosy and should be enrolled in studies focusing on alternative targets to improve the management of leprosy and its reactions.

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Serum thrombomodulin

Cited by 45 publications

References 14 publications

The Multifunctional Protein C System

The Multifunctional Protein C System

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

The involvement of endothelial mediators in leprosy

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