28 research outputs found
Roles of Coagulation Proteases and PARs (Protease-Activated Receptors) in Mouse Models of Inflammatory Diseases
Activation of the blood coagulation cascade leads to fibrin deposition and platelet activation that are required for hemostasis. However, aberrant activation of coagulation can lead to thrombosis. Thrombi can cause tissue ischemia, and fibrin degradation products and activated platelets can enhance inflammation. In addition, coagulation proteases activate cells by cleavage of PARs (protease-activated receptors), including PAR1 and PAR2. Direct oral anticoagulants have recently been developed to specifically inhibit the coagulation proteases FXa (factor Xa) and thrombin. Administration of these inhibitors to wild-type mice can be used to determine the roles of FXa and thrombin in different inflammatory diseases. These results can be compared with the phenotypes of mice with deficiencies of either Par1 (F2r) or Par2 (F2rl1). However, inhibition of coagulation proteases will have effects beyond reducing PAR signaling, and a deficiency of PARs will abolish signaling from all proteases that activate these receptors. We will summarize studies that examine the roles of coagulation proteases, particularly FXa and thrombin, and PARs in different mouse models of inflammatory disease. Targeting FXa and thrombin or PARs may reduce inflammatory diseases in humans
Differential roles of factors IX and XI in murine placenta and hemostasis under conditions of low tissue factor
The intrinsic tenase complex (FIXa-FVIIIa) of the intrinsic coagulation pathway and, to a lesser extent, thrombin-mediated activation of FXI, are necessary to amplify tissue factor (TF)-FVIIa-initiated thrombin generation. In this study, we determined the contribution of murine FIX and FXI to TF-dependent thrombin generation in vitro. We further investigated TF-dependent FIX activation in mice and the contribution of this pathway to hemostasis. Thrombin generation was decreased in FIX- but not in FXI-deficient mouse plasma. Furthermore, injection of TF increased levels of FIXa-antithrombin complexes in both wildtype and FXI-/- mice. Genetic studies were used to determine the effect of complete deficiencies of either FIX or FXI on the survival of mice expressing low levels of TF. Low-TF; FIX2/y male mice were born at the expected frequency, but none survived to wean. In contrast, low-TF;FXI-/- mice were generated at the expected frequency at wean and had a 6-month survival equivalent to that of low-TF mice. Surprisingly, a deficiency of FXI, but not FIX, exacerbated the size of blood pools in low-TF placentas and led to acute hemorrhage and death of some pregnant dams. Our data indicate that FIX, but not FXI, is essential for survival of low-TF mice after birth. This finding suggests that TF-FVIIa-mediated activation of FIX plays a critical role in murine hemostasis. In contrast, FXI deficiency, but not FIX deficiency, exacerbated blood pooling in low-TF placentas, indicating a tissue-specific requirement for FXI in the murine placenta under conditions of low TF
Kenproblemen in de discussie over geloof, respect, diversiteit en pluraliteit op school en in het onderwijsbeleid. Een slotbeschouwing
Long-term estrogen treatment of mice with a prothrombotic phenotype induces sustained increases in thrombin generation without affecting tissue fibrin deposition
Thrombosis and Hemostasi
The Intrinsic Pathway does not Contribute to Activation of Coagulation in Mice Bearing Human Pancreatic Tumors Expressing Tissue Factor
Atrial fibrillation progression risk factors and associated cardiovascular outcome in well-phenotyped patients:data from the AF-RISK study
Use of "C9/11 Mismatch" Control Small Interfering RNA Reveals Sequence-Related Off-Target Effect on Coagulation of an Small Interfering RNA Targeting Mouse Coagulation Factor XII
Thrombosis and Hemostasi
Associations Between Thrombin Generation and the Risk of Cardiovascular Disease in Elderly Patients: Results From the PROSPER Study
Cardiolog
Vascular Function, Systemic Inflammation, and Coagulation Activation 18 Months after COVID-19 Infection: An Observational Cohort Study
Characterization of hemostasis in mice lacking the novel thrombosis susceptibility gene Slc44a2
Thrombosis and Hemostasi