Changes in thrombomodulin level in plasma of endotoxin-infused rabbits

Sawada, Kazuyoshi; Yamamoto, Hitoshi; Matsumoto, Kenji; Yago, Hisashi; Suehiro, Seishi; Tahara, Chieko; Ishii, Hidemi; Kazama, Mutsuyoshi; Abe, Takeshi

doi:10.1016/0049-3848(92)90240-b

Cited by 14 publications

(3 citation statements)

References 22 publications

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“…Serum TM is used as a biomarker of endothelial cell injury. In vitro and ex vivo studies have shown that endothelial injury decreases TM expression in the endothelium and increases the level of TM in culture or perfusion media Sawada et al 1992;Miyazaki et al 1998;Boehme et al 2002). These results indicate that TM is shed because of injury and that soluble TM is released into the surrounding media.…”

Section: Discussionmentioning

confidence: 55%

“…TM has been utilized as a biomarker of endothelial cell injury in vitro and ex vivo Sawada et al 1992;Miyazaki et al 1998;Boehme et al 2002). Many studies have shown elevated levels of serum TM among patients with disseminated intravascular coagulopathy, diabetes mellitus, systemic lupus erythematosus, and a variety of collagen-vascular diseases (Takano et al 1990;Tanaka et al 1991;Wada et al 1993;Ohdama et al 1994).…”

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confidence: 99%

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Serum Thrombomodulin as a Newly Identified Biomarker for Postoperative Lung Injury: A Prospective Observational Study

Maeda

Takahashi

Sato

2012

Tohoku J. Exp. Med.

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Postoperative lung injury after lung cancer resection is still a difficult problem to be solved. Thrombomodulin (TM) is a membrane-bound glycoprotein of endothelial cells, and its serum level is elevated in patients with acute lung injury or acute respiratory distress syndrome. In fact, TM is abundant in the pulmonary capillary vessels. Lung resection reduces the volume of pulmonary capillary vessels; however, the change in the serum levels of TM after lung resection remains to be investigated. We therefore analyzed the postoperative changes in the serum TM levels in 60 patients who underwent thoracotomy without lung resection (n = 3), partial resection of the lung (n = 15), or lobectomy (n = 42). Preoperative and postoperative day-1 laboratory data including the serum levels of TM and KL-6, a sialylated carbohydrate antigen (a biomarker for pulmonary fibrosis), and oxygenation index were collected. Unexpectedly, the postoperative serum levels of TM were lower than preoperative values in lobectomy group, whereas they remained unchanged after thoracotomy without lung resection and after partial resection of the lung. In addition, the serum TM level decreased proportional to the resected lung volume. Eight out of 42 patients with lobectomy presented high postoperative serum levels of TM, and 3 out of these 8 patients presented postoperative impaired oxygenation. Postoperative impaired oxygenation occurred only in patients with elevated TM levels; namely, an increase of serum TM is associated with impaired oxygenation after lung resection. In conclusion, serum TM is a possible biomarker for predicting the occurrence of postoperative lung injury.

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Section: Discussionmentioning

confidence: 55%

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confidence: 99%

Serum Thrombomodulin as a Newly Identified Biomarker for Postoperative Lung Injury: A Prospective Observational Study

Maeda

Takahashi

Sato

2012

Tohoku J. Exp. Med.

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“…Plasma procarboxypeptidase B activation is preferentially accelerated by high concentrations of thrombin and low concentrations of thrombomodulin and is reduced at high thrombomodulin concentrations [16], whereas protein C is activated by low thrombin concentrations and high thrombomodulin concentrations [9, 17]. Furthermore, endothelial cells exposed to LPS downregulate the thrombomodulin expression and upregulate the tissue factor expression, a trigger of thrombin generation in the coagulation cascade, on the cell surface during transcriptional modification of these factors [18,19,20]. Thus, the present thrombotic glomerulonephritis model could be considered at high thrombin and low thrombomodulin concentrations on the endothelial surface to preferentially activate plasma procarboxypeptidase B.…”

Section: Discussionmentioning

confidence: 99%

EF6265, a Novel Plasma Carboxypeptidase B Inhibitor, Protects against Renal Dysfunction in Rat Thrombotic Glomerulonephritis through Enhancing Fibrinolysis

Muto

Suzuki

Iida

et al. 2007

Nephron Exp Nephrol

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Background/Aim: Plasma carboxypeptidase B is a physiological fibrinolysis inhibitor. In the present study, the effects of EF6265, a novel specific plasma carboxypeptidase B inhibitor, on renal dysfunction in a rat thrombotic glomerulonephritis model were examined. Methods: The model was induced by injection of anti-glomerular basement membrane serum and lipopolysaccharide to rats. Renal microthrombosis was histologically evaluated by phosphotungstic acid-hematoxylin staining for fibrin thrombi. Renal dysfunction was evaluated on the basis of plasma levels of blood urea nitrogen as well as renal edemas and urine volume. Results: The glomerular microthrombi observed in a positive control group were significantly reduced after a short-term treatment (4 h) with EF6265 at a dose which enhanced fibrinolysis. The elevation of blood urea nitrogen and renal edema formation decreased, and the reduction of the urine volume improved after a long-term treatment (21 h) with EF6265. In addition, EF6265 had a protective activity against multiple organ dysfunction, because it reduced plasma lactate dehydrogenase and alanine aminotransferase levels and mortality in this model. Conclusion: EF6265, which inhibits plasma carboxypeptidase B, showed a protective effect on thrombotic renal dysfunction in thrombotic glomerulonephritis through enhancing the fibrinolysis.

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