Increasing post-event plasma thrombomodulin level associates with worse outcome in survival of acute coronary syndrome

Chan, Shih-Hung; Chen, Jyh-Hong; Li, Yi‐Heng; Lin, Long-Yau; Tsai, Liang‐Miin

doi:10.1016/j.ijcard.2005.09.015

Cited by 20 publications

(17 citation statements)

References 18 publications

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“…35 Studies of recombinant TM proteins or native soluble TM fragments from body fluid suggested that soluble TM not only serves as a marker for endothelial damage, but also has some physiologic or pathophysiologic effects. The recombinant EGF-like domain of TM (TM domain 2, rTMD2) has a mitogenic effect on several cell types, including smooth muscle cells and Swiss 3T3 cells.…”

Section: Discussionmentioning

confidence: 99%

The recombinant lectin-like domain of thrombomodulin inhibits angiogenesis through interaction with Lewis Y antigen

Kuo

Chen

Chang

et al. 2012

Blood

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IntroductionAngiogenesis is involved in physiologic processes such as embryogenesis, wound healing, and the female reproductive cycle, and also contributes to the pathogenesis of numerous disorders, including atherosclerosis, ischemic disease, arthritis, and cancer. 1 Normally, angiogenesis is strictly controlled by the balance between angiogenic promoters and inhibitors.Thrombomodulin (TM) is a type I-glycosylated membrane protein composed of 5 distinct domains. At the NH 2 -terminal is a C-type lectin-like domain followed by 6 consecutively repeated epidermal growth factor (EGF)-like domains and an O-glycosylation site-rich domain. Connected to these extracellular domains is a transmembrane domain followed by a short cytoplasmic tail. 2 TM functions as part of the anticoagulant pathway; it binds thrombin on the cell surface and catalyzes proteolytic activation of protein C. 2 Soluble TM fragments have been detected in the medium of cultured TM-expressing cells 3 and human plasma and urine, 4-6 but the physiologic significance of the soluble TM fragments remains unclear. Our previous study showed that the recombinant EGF-like domain plus the O-glycosylation site-rich domain of TM (rTMD23) promotes angiogenesis in vitro and in vivo. 7 The multiple mechanisms underlying the anti-inflammatory activity of the recombinant lectin-like domain of TM have been demonstrated recently. [8][9][10][11] Lewis Y Ag (LeY) belongs to the type II Lewis Ag family, which is structurally related to the determinants of the ABH blood group system. LeY is expressed on the cell membrane along with phospholipids, 12 EGF receptors, 13 and mucins, 14 and its soluble form is up-regulated in the synovial fluid of human angiogenic rheumatoid arthritis. 15 LeY has been suggested to be a participant in cell-cell interaction, 16 arthritis, 15 and cancer. 17 In addition, ablation in endothelial cells of fucosyltransferase I, which is crucial for generation of the precursor of type II Lewis Ag, resulted in defective tube formation, suggesting the role of LeY in endothelial cell-cell contacts. 18 Previously, we demonstrated that recombinant lectin-like domain of TM (rTMD1) suppressed lipopolysaccharide-induced inflammation through interaction with LeY-conjugated lipopolysaccharide. 11 However, the biologic significance of the interaction between rTMD1 and LeY on the endothelial cell surface has never been investigated. In this study, the biologic function of LeY on endothelial cells and the antiangiogenic function of rTMD1 were investigated. In addition, recombinant adeno-associated virus (AAV) expression vector carrying TMD1 (AAV-TMD1) resulted in efficient suppression of angiogenesis with a single injection of AAV in mice. An Inside Blood analysis of this article appears at the front of this issue.The online version of this article contains a data supplement.The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance ...

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Section: Discussionmentioning

confidence: 99%

The recombinant lectin-like domain of thrombomodulin inhibits angiogenesis through interaction with Lewis Y antigen

Kuo

Chen

Chang

et al. 2012

Blood

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“…Increased sTM level has been associated with mortality in patients with trauma, acute respiratory distress syndrome, major surgery and sepsis, expressing a correlation with multiple organ failure [5][6][7]. Moreover, increased sTM in patients with atherosclerosis is a predictor of poor cardiovascular outcome and increased levels of sTM, C-reactive protein (CRP) and another inflammatory markers have been reported after percutaneous coronary interventions [15] and have been found to be a predictor of poor outcome in patients surviving acute coronary syndromes [4].…”

Section: Discussionmentioning

confidence: 99%

“…It is released into serum by proteolytic degradation of endothelial cells after injury by oxidative stress products, such as hydrogen peroxide, or by activated leukocytes [2,3]. Clinically, elevated sTM has been found to predict events in patients surviving an acute coronary syndrome [4], and increased sTM level has been reported in patients with multiple organ dysfunction syndrome (MODS), disseminated intravascular coagulation induced by sepsis or blunt trauma. In all these conditions, sTM has been associated with increased mortality [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

“…In all these conditions, sTM has been associated with increased mortality [5][6][7]. Therefore, it has been suggested that the elevation of sTM levels might be associated with a higher inflammatory state [4,8,9]. Cardiac surgery with cardiopulmonary bypass (CPBP) is associated with a systemic inflammatory response similar to that observed in all these conditions, and leukocytosis with neutrophilia frequently occurs in this scenario [10].…”

Section: Introductionmentioning

confidence: 99%

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Soluble Thrombomodulin Levels are Related to Inflammation after Coronary Bypass Surgery

Arazi¹

2011

J Clinic Experiment Cardiol

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Background: Soluble Thrombomodulin (sTM) is released from endothelial cells after injury by activated leukocytes in inflammatory states and it has been associated with worse prognosis in inflammatory conditions. The purpose of this study was to analyze the association between levels of sTM and inflammation and to describe the possible explanations about association between sTM and post-operative complications. Methods and Materials:We measured levels of sTM, IL6 and leukocytes in different moments during the first month in 18 patients after coronary by-pass graft surgery. Chisquare test and Fisher test were used for categorical variables. For continuous variables we used either Student t test or Wilcoxon rank-sum test depending on whether the data were normally distributed. Results:The levels of sTM increased during the first post-surgery week, and then decreased to values similar to those recorded pre-operatively. IL6 peaked at after 24 hours, and significantly correlated with white blood cell count (Spearman 0.69, p=<0.0001). There was a significant association between sTM at T3 and white blood cells count at T1 (p=0.01224). Two patients had three or more post-operative complications, and they presented higher levels of sTM. Conclusions:We found a transient increase in sTM during the first week after CABG associated with an inflammatory response and leukocytosis. These changes could imply endothelial dysfunction after surgery and may represent prognostic factors for outcomes.

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“…Patients with autoimmune diseases, 7,8 renal failure creatinine Cr 2.0 mg / dl 9 , current or previous arterial thrombosis [10][11][12][13] , or liver failure 14,15 , all of which can affect serum sTM concentrations, were excluded from the study. After hospitalization, anticoagulant therapy was administered to all patients and thrombolysis was performed in patients with unstable hemodynamics or those who were considered by their attending physicians to need such therapy.…”

Section: Methodsmentioning

confidence: 99%

Serum Soluble Thrombomodulin Level on Admission Is a Useful Predictor of Treatment Response in Patients with Acute Pulmonary Thromboembolism

:筆頭著者

Miyake

et al. 2017

Showa Univ J Med Sci

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: Previous studies have reported elevated serum soluble thrombomodulin sTM concentrations in acute pulmonary thromboembolism APTE , but no study has evaluated the relationship between the serum sTM concentration and prognosis. In the present study we investigated the correlation between the serum sTM concentration on admission and the duration of oxygen supplementation in patients admitted to the coronary care unit CCU for APTE to evaluate whether serum sTM is a useful predictor of treatment response. The study included 38 consecutive patients 14 men, 24 women ; mean SD age 59.9 16.8 years admitted to the CCU between March 2012 and July 2014 with a diagnosis of APTE con rmed by contrast-enhanced computed tomography within 7 days of onset. The severity of pulmonary embolism was classi ed as collapse and cardiac arrest type in three patients 8 , massive type in two 5 , submassive type in 19 50 , and nonmassive type in 14 38 . Signi cant positive correlations were found for both age and creatinine clearance with duration of hospitalization, but not with duration of oxygen supplementation. There was a signi cant positive correlation between admission sTM concentrations and both days of hospitalization R 0.57, P 0.005 and duration of oxygen supplementation R 0.56, P 0.01 . The ndings of the present study suggest that serum sTM concentrations are promising predictors of treatment response and short-term prognosis in patients with APTE.

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Increasing post-event plasma thrombomodulin level associates with worse outcome in survival of acute coronary syndrome

Cited by 20 publications

References 18 publications

The recombinant lectin-like domain of thrombomodulin inhibits angiogenesis through interaction with Lewis Y antigen

The recombinant lectin-like domain of thrombomodulin inhibits angiogenesis through interaction with Lewis Y antigen

Soluble Thrombomodulin Levels are Related to Inflammation after Coronary Bypass Surgery

Serum Soluble Thrombomodulin Level on Admission Is a Useful Predictor of Treatment Response in Patients with Acute Pulmonary Thromboembolism

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