Endothelial cells and leukocytes in hemostasis and thrombosis

Question 1

Intact endothelial cells are antithrombotic
-> What is the role of NO, PGI2, ectoADPase?

Answer 1

They inhibit platelet aggregation

Question 2

Intact endothelial cells are antithrombotic
-> What is the role of TM/ProtC-pathway, heparan-sulfate?

Answer 2

They limits fibrin formation

Question 3

Intact endothelial cells are antithrombotic
-> What is the role of tPA?

Answer 3

It initiates fibrinolysis

Question 4

What is the general role of Intact endothelial cells?

Answer 4

Shields thrombogenic material in the vessel wall from flowing blood

Question 5

Heparan-sulfate on the surface of endothelial cells accelerates ___

Answer 5

thrombin inactivation by antithrombin (just like heparin)

Question 6

NO inhibits ___

Answer 6

NO inhibits platelet aggregation just like smooth muscle cell contraction (cGMP↑, Ca2+↓)

Question 7

What does this slide indicate?

Answer 7

The TM(Thrombomodulin)-PC(Protein C) anticoagulant pathway

Question 8

Altered blood flow can disturb the behaviour of ____

Answer 8

endothelial cells

Question 9

3 Interactions between leukocytes and hemostasis/thrombosis

Answer 9

1. Coagulation may activate leukocytes
2. Cell adhesion receptors
3. Leukocytes may induce a prothrombotic shift

Question 10

Interactions between leukocytes and hemostasis/thrombosis
-> 1. Coagulation may activate leukocytes
-> Examples of the substances that can be involved?

Answer 10

eg. Fibrinopeptides, FDP, thrombin

Question 11

Interactions between leukocytes and hemostasis/thrombosis
-> 2. Cell adhesion receptors
-> Explain

Answer 11

Direct interactions among platelets, leukocytes and endothelial cells (P-selectin, integrins, adhesive proteins in the vessel wall, Fg, VWF)

Question 12

Interactions between leukocytes and hemostasis/thrombosis

-> Leukocytes may induce a prothrombotic shift
-> How?

Answer 12

• Cytokines effect endothelial cells
• NET-formation with DNA, histones, and others

Question 13

What is NET (neutrophil extracellular trap)?

Answer 13

Part of the innate immune system: localization and killing of pathogens

Question 14

How does NET (neutrophil extracellular trap) work In activated neutrophils?

Answer 14

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

Question 15

What is „citrullination”?

Answer 15

positive charge of Arg lost

Question 16

4 causes of venous thrombosis?

Answer 16

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

Question 17

Does Low shear favor platelet deposition?

Answer 17

NO

Question 18

Does Low shear favor thrombin-dependent fibrin formation?

Answer 18

YES

Question 19

Therapeutic targets in the Fibrin/NET/vWF -Complex
-> What are the substances against histones?

Answer 19

Heparin, vitamin K-antagonists, NOAC, Aspirin, Ticlopidin, tPA activated Protein C

Question 20

Therapeutic targets in the Fibrin/NET/vWF -Complex
-> What are the substances against DNS?

Answer 20

Dnase

Question 21

Therapeutic targets in the Fibrin/NET/vWF -Complex
-> What is the role of P-Selectin blockers?

Answer 21

To prevent adhesion of platelets, leukocytes