Blood Coagulation and Thrombosis Mechanisms

Mapping the Mutational Landscape for Streptokinase Binding to Plasminogen

This study maps the mutational landscape of streptokinase (SK) from Group C Streptococcus to identify amino acid substitutions affecting its binding to human plasminogen.

ApoE4 Promotes Thrombosis via Endothelial Cell ApoER2 and PP2A Activation

This study identifies APOE4 as a risk factor for thrombosis by promoting vWF secretion through ApoER2 and PP2A activation in endothelial cells, leading to increased thrombosis in mice and human veins.

Modeling the Role of Platelet-Released Polyphosphates in Tissue-Factor-Initiated Coagulation under Flow

This study models how polyphosphate from activated platelets affects thrombin generation in tissue-factor-initiated coagulation under flow conditions.

Lipoprotein(a) promotes thrombosis through platelet activation and promotion of a lysis-resistant thrombus architecture

This study shows that lipoprotein(a) promotes thrombosis by enhancing platelet activation and creating lysis-resistant thrombus structures, with effects mitigated by aspirin.

Investigating the structural effects of anti-thrombin anticoagulant aptamers on activation of human prothrombin

This study investigates how anti-thrombin aptamers affect prothrombin activation by analyzing their structural interactions and binding effects.

Lack of canonical PAR4 activation is associated with reduced arterial and venous thrombosis in mice.

This study creates a mouse model with a thrombin-insensitive PAR4 receptor, showing reduced thrombosis but normal responses to PAR4 agonists.

A Procoagulant Peptide Analog of the SARS-CoV-2 Nucleocapsid C-terminal Domain

The paper tests a procoagulant peptide analog of the SARS-CoV-2 N-terminal domain in plasma coagulation assays, showing it significantly reduces clotting time.

Biochemical and Immunological Properties of Engineered Low-Immunogenic Staphylokinases for Next-Generation Thrombolytic Therapy

The paper compares biochemical and immunological properties of engineered low-immunogenic staphylokinase variants to identify the most promising for thrombolytic therapy.

Protease-Activated Receptor 1 as an Endogenous Model of Peptidergic Gαq-Gα12-Biased G Protein Signaling

This paper investigates how different proteases shape G protein signaling through PAR1, showing thrombin activates Gq and G12 while aPC only activates G12, with distinct transcriptional and physiological outcomes.

A sensitized model of thrombosis validates known multigenic relationships and suggests novel modifiers of hemostasis

This paper uses a zebrafish model to identify genetic modifiers of thrombosis, finding a novel mutation in prothrombin and additional modifiers like factor X and plasminogen.

Prothrombinase processivity is conferred by substrate allostery

The paper presents cryo-EM structures of prothrombinase complexed with prothrombin and meizothrombin, revealing substrate allostery as the mechanism for processive cleavage.

Structure of Factor VII Gla domain bound to EPCR

The paper reports the crystal structure of factor VII Gla domain bound to EPCR, revealing structural insights into their binding and competition with PC-EPCR.

Computational modeling of pro-inflammatory cytokine-enhanced blood coagulation

This study develops a computational model linking pro-inflammatory cytokines to coagulation dynamics, showing how inflammation alters thrombin generation in different diseases.

POmAb, an antibody targeting open prothrombin, results in anticoagulation without excessive bleeding in mice

This study evaluates POmAb, an anti-prothrombin antibody, in mice showing it reduces thrombin generation and fibrin formation without excessive bleeding.

A Sensitized ENU Mutagenesis Screen for Thrombosis Modifiers Identifies Suppressor Variants in Non-mutagenized Parental Generations Due to Antithrombotic Selective Pressures

The paper identifies four spontaneous mutations that confer survival in a thrombosis model by reducing platelet aggregation and altering gene expression.

Structure-function studies on the serine protease domain of Factor VII activating protease (FSAP).

This paper investigates how mutations in FSAP's serine protease domain affect its substrate cleavage and inhibitor resistance, identifying key residues involved in function and inhibition.

Engineering a membrane-independent human prothrombinase through parsimonious mutation of factor Xa

This study creates a PL-independent human prothrombinase by mutating factor Xa to mimic the high-affinity binding of HopD to fVa, achieving a Kd of ~20 nM.

Pro-coagulant lipids in physiological ratios found in the activated platelet membrane do not impact clot structure or fibrinolysis in purified assays.

The paper tests the effect of pro-coagulant lipids on clot structure and fibrinolysis using physiological ratios and finds no significant impact.

Inhibiting monocyte migration reduces arterial thrombosis and facilitates thrombolysis

This study shows that inhibiting monocyte migration via CCR2 deficiency reduces arterial thrombosis and improves thrombolysis in mice.

Structural Insights into Zn2+ and Ca2+ binding to Human Protein Z and Their Impact on Membrane Association

This study investigates how Ca2+ and Zn2+ bind to human protein Z, affecting its structure and membrane association, and their impact on PZ-ZPI complex stability.

Identification of Regulatory Loci for Megakaryocyte and Hepatocyte Coagulation Factor V Expression in Mice

The paper identifies genomic loci regulating Factor V expression in hepatocytes and megakaryocytes of mice using QTL analysis across multiple strains.

The Main protease (Mpro) from SARS-CoV-2 triggers plasma clotting in vitro by activating coagulation factors VII and FXII

This study shows that SARS-CoV-2 main protease (Mpro) activates coagulation factors VII and XII, increasing plasma clotting probability by 2.5-fold.

A novel function for endothelial protease-activated receptors in modulating insulin receptor activity with implications for diabetes

This study shows that endothelial PAR1/4 deletion increases insulin sensitivity and protects against diabetes by enhancing insulin receptor activity through reduced PTP1B activity.

Caffeic acid promoted deep vein thrombosis resolution in mice by suppressed macrophage M1 polarization through Keap1/Nrf2 pathwayv

This study shows that caffeic acid promotes DVT resolution in mice by suppressing macrophage M1 polarization through the Keap1/Nrf2 pathway.

Human PAR1 expressed on mouse platelets contributes to hemostasis and arterial occlusion

This paper demonstrates that human PAR1 expressed in mouse platelets affects hemostasis and arterial occlusion, with vorapaxar reversing these effects.

Potassium ferric oxalate nanoparticles prevent human blood clotting and thrombosis in a mouse model

This study demonstrates that potassium ferric oxalate nanoparticles inhibit blood clotting and thrombosis in a mouse model by chelating calcium ions and hindering factor XII activation.

Direct Optical Detection of Factor Xa Activity in Minimally Processed Whole Blood

This paper develops an optical method to directly detect factor Xa activity in whole blood, enabling rapid anticoagulant monitoring and personalized treatment.

Prothrombin prevents fatal T cell-dependent anemia during chronic virus infection of mice

This study shows that prothrombin prevents fatal T cell-dependent anemia in mice during chronic viral infection by reducing hemolysis, not by affecting T cell function or viral load.

Mice with Reduced PAR4 Reactivity show Decreased Venous Thrombosis and Platelet Procoagulant Activity

This study shows that mice with a PAR4 mutation (PAR4-P322L) have reduced venous thrombosis and platelet procoagulant activity due to decreased phosphatidylserine exposure and thrombin generation.

Andexanet alfa-associated heparin resistance in cardiac surgery: mechanism and in vitro perspectives

This study investigates how andexanet alfa causes heparin resistance in cardiac surgery, showing it sequesters heparin-bound antithrombin and creates a triphasic response to heparin.