Thrombomodulin: A Bifunctional Modulator of Inflammation and Coagulation in Sepsis
Deregulated interplay between inflammation and coagulation plays a pivotal role in the pathogenesis of sepsis. Therapeutic approaches that simultaneously target both inflammation and coagulation hold great promise for the treatment of sepsis. Thrombomodulin is an endogenous anticoagulant protein tha...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Critical Care Research and Practice |
| Online Access: | http://dx.doi.org/10.1155/2012/614545 |
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| _version_ | 1832553596081668096 |
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| author | Takayuki Okamoto Hironobu Tanigami Koji Suzuki Motomu Shimaoka |
| author_facet | Takayuki Okamoto Hironobu Tanigami Koji Suzuki Motomu Shimaoka |
| author_sort | Takayuki Okamoto |
| collection | DOAJ |
| description | Deregulated interplay between inflammation and coagulation plays a pivotal role in the pathogenesis of sepsis. Therapeutic approaches that simultaneously target both inflammation and coagulation hold great promise for the treatment of sepsis. Thrombomodulin is an endogenous anticoagulant protein that, in cooperation with protein C and thrombin-activatable fibrinolysis inhibitor, serves to maintain the endothelial microenvironment in an anti-inflammatory and anticoagulant state. A recombinant soluble form of thrombomodulin has been approved to treat patients suffering from disseminated intravascular coagulation (DIC) and has thus far shown greater therapeutic potential than heparin. A phase II clinical trial is currently underway in the USA to study the efficacy of thrombomodulin for the treatment of sepsis with DIC complications. This paper focuses on the critical roles that thrombomodulin plays at the intersection of inflammation and coagulation and proposes the possible existence of interactions with integrins via protein C. Finally, we provide a rationale for the clinical application of thrombomodulin for alleviating sepsis. |
| format | Article |
| id | doaj-art-29702903315d4081abee9b3494506119 |
| institution | Kabale University |
| issn | 2090-1305 2090-1313 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Critical Care Research and Practice |
| spelling | doaj-art-29702903315d4081abee9b34945061192025-02-03T05:53:39ZengWileyCritical Care Research and Practice2090-13052090-13132012-01-01201210.1155/2012/614545614545Thrombomodulin: A Bifunctional Modulator of Inflammation and Coagulation in SepsisTakayuki Okamoto0Hironobu Tanigami1Koji Suzuki2Motomu Shimaoka3Department of Molecular Pathobiology and Cell Adhesion Biology, Graduate School of Medicine, Mie University, 2-174 Edobashi, Tsu 514-8507, JapanDepartment of Anesthesiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi, Higashinari-ku, Osaka 537-8511, JapanDepartment of Molecular Pathobiology and Cell Adhesion Biology, Graduate School of Medicine, Mie University, 2-174 Edobashi, Tsu 514-8507, JapanDepartment of Molecular Pathobiology and Cell Adhesion Biology, Graduate School of Medicine, Mie University, 2-174 Edobashi, Tsu 514-8507, JapanDeregulated interplay between inflammation and coagulation plays a pivotal role in the pathogenesis of sepsis. Therapeutic approaches that simultaneously target both inflammation and coagulation hold great promise for the treatment of sepsis. Thrombomodulin is an endogenous anticoagulant protein that, in cooperation with protein C and thrombin-activatable fibrinolysis inhibitor, serves to maintain the endothelial microenvironment in an anti-inflammatory and anticoagulant state. A recombinant soluble form of thrombomodulin has been approved to treat patients suffering from disseminated intravascular coagulation (DIC) and has thus far shown greater therapeutic potential than heparin. A phase II clinical trial is currently underway in the USA to study the efficacy of thrombomodulin for the treatment of sepsis with DIC complications. This paper focuses on the critical roles that thrombomodulin plays at the intersection of inflammation and coagulation and proposes the possible existence of interactions with integrins via protein C. Finally, we provide a rationale for the clinical application of thrombomodulin for alleviating sepsis.http://dx.doi.org/10.1155/2012/614545 |
| spellingShingle | Takayuki Okamoto Hironobu Tanigami Koji Suzuki Motomu Shimaoka Thrombomodulin: A Bifunctional Modulator of Inflammation and Coagulation in Sepsis Critical Care Research and Practice |
| title | Thrombomodulin: A Bifunctional Modulator of Inflammation and Coagulation in Sepsis |
| title_full | Thrombomodulin: A Bifunctional Modulator of Inflammation and Coagulation in Sepsis |
| title_fullStr | Thrombomodulin: A Bifunctional Modulator of Inflammation and Coagulation in Sepsis |
| title_full_unstemmed | Thrombomodulin: A Bifunctional Modulator of Inflammation and Coagulation in Sepsis |
| title_short | Thrombomodulin: A Bifunctional Modulator of Inflammation and Coagulation in Sepsis |
| title_sort | thrombomodulin a bifunctional modulator of inflammation and coagulation in sepsis |
| url | http://dx.doi.org/10.1155/2012/614545 |
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