Endothelial cells and leukocytes in hemostasis and thrombosis Flashcards
Intact endothelial cells are antithrombotic
-> What is the role of NO, PGI2, ectoADPase?
They inhibit platelet aggregation
Intact endothelial cells are antithrombotic
-> What is the role of TM/ProtC-pathway, heparan-sulfate?
They limits fibrin formation
Intact endothelial cells are antithrombotic
-> What is the role of tPA?
It initiates fibrinolysis
What is the general role of Intact endothelial cells?
Shields thrombogenic material in the vessel wall from flowing blood
Heparan-sulfate on the surface of endothelial cells accelerates ___
thrombin inactivation by antithrombin (just like heparin)
NO inhibits ___
NO inhibits platelet aggregation just like smooth muscle cell contraction (cGMP↑, Ca2+↓)
What does this slide indicate?
The TM(Thrombomodulin)-PC(Protein C) anticoagulant pathway
Altered blood flow can disturb the behaviour of ____
endothelial cells
3 Interactions between leukocytes and hemostasis/thrombosis
- Coagulation may activate leukocytes
- Cell adhesion receptors
- Leukocytes may induce a prothrombotic shift
Interactions between leukocytes and hemostasis/thrombosis
-> 1. Coagulation may activate leukocytes
-> Examples of the substances that can be involved?
eg. Fibrinopeptides, FDP, thrombin
Interactions between leukocytes and hemostasis/thrombosis
-> 2. Cell adhesion receptors
-> Explain
Direct interactions among platelets, leukocytes and endothelial cells (P-selectin, integrins, adhesive proteins in the vessel wall, Fg, VWF)
Interactions between leukocytes and hemostasis/thrombosis
-> Leukocytes may induce a prothrombotic shift
-> How?
- Cytokines effect endothelial cells
- NET-formation with DNA, histones, and others
What is NET (neutrophil extracellular trap)?
Part of the innate immune system: localization and killing of pathogens
How does NET (neutrophil extracellular trap) work In activated neutrophils?
NADPH oxidase, ROS-formation, PAD-activation (peptidyl-arginine-
deimináz, arginin is converted to citrullin, positive charge lost), proteins are modified.
Membrane disintegration, chromatin decondensation and expulsion from the cells together with other antimicrobal compounds.
DNA- histone nets localize bacteria, prevent spreading
What is „citrullination”?
positive charge of Arg lost
4 causes of venous thrombosis?
1, problems with venous valves– slow or turbulent blood flow
2, Hypoxia and abnormal blood flow disturbs endothelial cells – prothrombotic shift
3, Inflammation and thrombosis – NETs are prothrombotic
4, Leukocytes and microparticles carry TF around
Does Low shear favor platelet deposition?
NO
Does Low shear favor thrombin-dependent fibrin formation?
YES
Therapeutic targets in the Fibrin/NET/vWF -Complex
-> What are the substances against histones?
Heparin, vitamin K-antagonists, NOAC, Aspirin, Ticlopidin, tPA activated Protein C
Therapeutic targets in the Fibrin/NET/vWF -Complex
-> What are the substances against DNS?
Dnase
Therapeutic targets in the Fibrin/NET/vWF -Complex
-> What is the role of P-Selectin blockers?
To prevent adhesion of platelets, leukocytes
