Background: During veno-venous extracorporeal membrane oxygenation (VV-ECMO), systemic anticoagulation is required to prevent thrombotic complications within the circuit and oxygenator. The unfractionated heparin (UFH) commonly administered as a standard anticoagulant, but in our institute recombinant human thrombomodulin (rhTM), instead of UFH, used an anticoagulant for VV-ECMO. In present stu...

BACKGROUND Although 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are known to modulate endothelial function, the transcriptional mechanisms underlying these effects are incompletely understood. We hypothesized that Lung-Kruppel-like factor (LKLF/KLF2), a novel and potent regulator of endothelial gene expression, may mediate the downstream effects of statins. Here we repo...

The crystallographic structure has been determined of a complex between a nonadecapeptide from the fifth epidermal growth factor (EGF5) domain of human thrombomodulin and human D-PheProArg-alpha-thrombin. The peptide corresponds to amino acid residues Glu408-Glu426 of thrombomodulin and contains the third disulfide loop of EGF5 and its linker to EGF6. The structure was refined at 3.0-A resoluti...

BACKGROUND Low levels of activated protein C (APC) are a risk factor for venous thrombosis. The mechanisms leading to interindividual differences in APC are not totally elucidated. Protein C is activated by the thrombin-thrombomodulin complex. As thrombin binds to fibrinogen and thrombomodulin through a common region, it is conceivable that fibrinogen influences the activation of protein C. Thi...

BACKGROUND The genes encoding proteins in the thrombomodulin-protein C pathway are promising candidate genes for stroke susceptibility because of their importance in thrombosis regulation and inflammatory response. Several published studies have shown that the Ala455Val thrombomodulin polymorphism is associated with ischemic heart disease, but none has examined the association with stroke. Usin...

A collection of 56 purified thrombin mutants, in which 76 charged or polar surface residues on thrombin were mutated to alanine, was used to identify key residues mediating the interactions of thrombin with thrombomodulin (TM), protein C, and thrombin-activatable fibrinolysis inhibitor (TAFI). Comparison of protein C activation in the presence and absence of TM identified 11 residues mediating ...

Ambrosi et al (1) recently reported levels of various endothelial markers in cardiac transplant recipients before and after being placed on the lipid-lowering agent fluvastatin. This intervention reduced levels of cholesterol and soluble thrombomodulin (both p <0.001) but, despite this, there was no difference in levels of von Willebrand factor. Our colleagues found this failure to respond puzz...

Exosite 1 of thrombin consists of a cluster of basic residues (Arg-35, Lys-36, Arg-67, Lys-70, Arg-73, Arg-75, and Arg-77 in chymotrypsinogen numbering) that play key roles in the function of thrombin. Structural data suggest that the side chain of Arg-35 projects toward the active site pocket of thrombin, but all other residues are poised to interact with thrombomodulin (TM). To study the role...

135 Received June 1, 2012; accepted September 3, 2012. Published online September 14, 2012; doi: 10.1620/tjem.228.135. Correspondence: Sumiko Maeda, M.D., Ph.D., Department of Thoracic Surgery, Tohoku University Hospital, 4-1 Seiryomachi, Aobaku, Sendai, Miyagi 980-8575, Japan. e-mail: [email protected] *Present address: Department of Thoracic Surgery, Tohoku University Hospital, 4-1 Seiry...