Increased Plasma Soluble Thrombomodulin Levels in Cardioembolic Stroke

Dharmasaroja, Permphan; Dharmasaroja, Pornpatr A.; Sobhon, Prasert

doi:10.1177/1076029611432744

Cited by 26 publications

(18 citation statements)

References 22 publications

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“…A recent study reported that, in patients presenting with sepsis, sICAM-1 and sVCAM-1 were accurately associated with organ dysfunction and mortality, which is consistent with our observation [5]. Furthermore, in addition to luminal cell adhesion molecules, diffuse capillary injury and consequential coagulation disorders play an important role in the pathogenesis of sepsis [3,24]. As a marker of endothelial injury and coagulation, sTM may be used in monitoring organ dysfunction syndromes in septic patients [15].…”

Section: Discussionsupporting

confidence: 88%

The role of biomarkers of endothelial activation in predicting morbidity and mortality in patients with severe sepsis and septic shock in intensive care: A prospective observational study

Fang

Shao

et al. 2018

Thrombosis Research

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Introduction: Endothelial dysfunction plays an essential role in the pathogenesis of sepsis. The study aimed to illustrate the associations between the dynamic change (from day 1 to day 7) in biomarker concentration of endothelial dysfunction and outcomes in severe sepsis and septic shock in the intensive care unit (ICU). Materials and methods:We studied 102 patients enrolled in the Beijing Chao-yang Hospital affiliated with the Capital Medical University. A receiver operating characteristic (ROC) curve were used to assess the prognostic values of the circulating adhesion Angiopoietin-2/Angiopoietin-1 ratio (Ang-2/Ang-1) and Angiopoietin-1/Tie-2 ratio (Ang-1/Tie-2), intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1 and thrombomodulin (TM). Spearman's rank correlation and a multiple regression analysis were used to assess the relationship between the change in sequential organ failure assessment (Δ SOFA) score (SOFA score at day 7 minus SOFA score at day 1) and the levels of Δ Ang-2/Ang-1 and Δ Ang-1/Tie-2 ratios, ΔsICAM-1, ΔsVCAM-1 and Δ sTM. Results: The Ang-2/Ang-1 ratio, sICAM-1, sVCAM-1 and sTM levels significantly increased from day 1 to day 7 (all p = 0.045), and the Ang-1/Tie-2 ratio level markedly decreased from day 1 and day 7 (p = 0.027) in nonsurvivors. The biomarkers at Days 1 and 7 had significant prognostic value for 90-day mortality in severe sepsis and septic shock in ICU. The difference in biomarkers for endothelial dysfunction were suggested to be effective, independent predictors of changes in Δ SOFA. Conclusions: Endothelial dysfunction may constitute an independent contributor to sepsis-associated outcomes in ICU. migrate into the surrounding tissue, and inflammation and coagulation pathways are activated. The key event underlying endothelial dysfunction is the massive response of the host to inflammatory mediators and pro-coagulant factors, contributing to endothelial injury, tissue hypoperfusion, disseminated intravascular coagulation and organ dysfunction [2].Abbreviations: Ang, angiopoietin; Tie-2, tyrosine kinase with immunoglobulin-like loop epidermal growth factor domain 2; Ang-2/Ang-1, Angiopoietin-2/ Angiopoietin-1 ratio; Ang-1/Tie-2, Angiopoietin-1/Tie-2 ratio; ICAM-1, intercellular adhesion molecule-1; VCAM-1, vascular cell adhesion molecule-1; TM, thrombomodulin; sICAM-1, soluble intercellular adhesion molecule-1; sVCAM-1, soluble vascular cell adhesion molecule-1; sTM, soluble thrombomodulin; ICU, intensive care unit; SOFA, sequential organ failure assessment; Δ SOFA score, SOFA score at day 7 minus SOFA score at day 1; Δ Ang-2/Ang-1 ratio, the level of Ang-2/Ang-1 ratio at day 7 minus the level of Ang-2/Ang-1 ratio at day 1; Δ Ang-1/Tie-2 ratio, the level of Ang-1/Tie-2 ratio at day 7 minus the level of Ang-1/Tie-2 ratio at day 1; Δ sICAM-1, the level of sICAM-1 at day 7 minus the level of sICAM-1 at day 1; Δ sVCAM-1, the level of sVCAM-1 at day 7 minus the level of sVCAM-1 at day 1; Δ sTM, the level of sTM at day 7 minus the level of sTM at day 1

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Section: Discussionsupporting

confidence: 88%

The role of biomarkers of endothelial activation in predicting morbidity and mortality in patients with severe sepsis and septic shock in intensive care: A prospective observational study

Fang

Shao

et al. 2018

Thrombosis Research

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“…As such, TM is a central determinant of vascular endothelial thromboresistance by promoting anti-coagulant and anti-inflammatory properties within the vessel wall [1]. Shedding or release of soluble TM (sTM) into circulating blood has also been widely reported [2]–[5].…”

Section: Introductionmentioning

confidence: 99%

Regulation of Thrombomodulin Expression and Release in Human Aortic Endothelial Cells by Cyclic Strain

et al. 2014

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Background and ObjectivesThrombomodulin (TM), an integral membrane glycoprotein expressed on the lumenal surface of vascular endothelial cells, promotes anti-coagulant and anti-inflammatory properties. Release of functional TM from the endothelium surface into plasma has also been reported. Much is still unknown however about how endothelial TM is regulated by physiologic hemodynamic forces (and particularly cyclic strain) intrinsic to endothelial-mediated vascular homeostasis.MethodsThis study employed human aortic endothelial cells (HAECs) to investigate the effects of equibiaxial cyclic strain (7.5%, 60 cycles/min, 24 hrs), and to a lesser extent, laminar shear stress (10 dynes/cm2, 24 hrs), on TM expression and release. Time-, dose- and frequency-dependency studies were performed.ResultsOur initial studies demonstrated that cyclic strain strongly downregulated TM expression in a p38- and receptor tyrosine kinase-dependent manner. This was in contrast to the upregulatory effect of shear stress. Moreover, both forces significantly upregulated TM release over a 48 hr period. With continuing focus on the cyclic strain-induced TM release, we noted both dose (0–7.5%) and frequency (0.5–2.0 Hz) dependency, with no attenuation of strain-induced TM release observed following inhibition of MAP kinases (p38, ERK-1/2), receptor tyrosine kinase, or eNOS. The concerted impact of cyclic strain and inflammatory mediators on TM release from HAECs was also investigated. In this respect, both TNFα (100 ng/ml) and ox-LDL (10–50 µg/ml) appeared to potentiate strain-induced TM release. Finally, inhibition of neither MMPs (GM6001) nor rhomboids (3,4-dichloroisocoumarin) had any effect on strain-induced TM release. However, significantly elevated levels (2.1 fold) of TM were observed in isolated microparticle fractions following 7.5% strain for 24 hrs.ConclusionsA preliminary in vitro investigation into the effects of cyclic strain on TM in HAECs is presented. Physiologic cyclic strain was observed to downregulate TM expression, whilst upregulating in a time-, dose- and frequency-dependent manner the release of TM.

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“…During endothelial pathologies, TM is released from the endothelium and can be detected in the serum in its soluble form. A significant increase in sTM level has been reported in vascular diseases, such as atherosclerosis, cardioembolic stroke, and sepsis-associated disseminated intravascular coagulation, indicating that sTM may represent a useful marker to assess endothelial dysfunction and vascular risk [22,23]. We also found increased levels of sTM in SCF subjects relative to controls, although the difference did not reach statistical significance.…”

Section: Discussionmentioning

confidence: 48%

Relationship between the endothelium biomarkers endocan and thrombomodulin and slow coronary flow

Baysal¹,

Koç²,

Kaya³

et al. 2018

biomedicalresearch

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Background: Growing evidence suggests that endothelial dysfunction plays a key role in the pathophysiology of Slow Coronary Flow (SCF). This study investigated the association between endothelial biomarkers endocan and soluble Thrombomodulin (sTM) and SCF. Methods: The study population consisted of 89 subjects (54 patients with SCF and 35 controls). Coronary flow rate was assessed using the Thrombolysis in Myocardial Infarction (TIMI) Frame Count (TFC) method. The serum endocan and sTM levels of all subjects were analysed. Results: Significantly higher endocan levels (1.14 ± 0.22 vs. 0.96 ± 0.32 ng/ml; p=0.009) and sTM levels (657.06 ± 198.18 vs. 592.76 ± 128.45 pg/ml; p=0.119) were observed in the SCF group relative to the control group. A positive correlation was detected between endocan and TFC (r=0.563; p=0.016). Multivariate logistic regression analysis revealed endocan as a predictor of SCF. Conclusions: The endocan level in SCF patients was significantly higher than in controls and the sTM level was also increased, although the difference was not significant. These results suggest that endocan may serve as a biomarker to predict SCF.

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Increased Plasma Soluble Thrombomodulin Levels in Cardioembolic Stroke

Cited by 26 publications

References 22 publications

The role of biomarkers of endothelial activation in predicting morbidity and mortality in patients with severe sepsis and septic shock in intensive care: A prospective observational study

The role of biomarkers of endothelial activation in predicting morbidity and mortality in patients with severe sepsis and septic shock in intensive care: A prospective observational study

Regulation of Thrombomodulin Expression and Release in Human Aortic Endothelial Cells by Cyclic Strain

Relationship between the endothelium biomarkers endocan and thrombomodulin and slow coronary flow

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