Vascular Endothelium 2

Question 1

What happens during the leukocyte adhesion cascade?

Answer 1

1. First start to roll along the endothelium and they spread and eventually find junctions to get through
2. This happens because the inflammatory agents have activated the endothelium to express molecules that support this process

Question 2

What does recruitment of blood leukocytes into tissues normally take place?

Answer 2

during inflammation

Question 3

Where do the leukocytes adhere to?

Answer 3

endothelium of post-capillary venules and transmigrate into tissues

Question 4

What is a capillary?

Answer 4

endothelial cells surrounded by basement membrane and pericapillary cells (pericytes)

Question 5

What is a post-capillary venule?

Answer 5

structure similar to capillaries but more pericytes

Question 6

How are capullary venules formed?

Answer 6

• by basically single endothelial cells within a few perictyes and basement membrane
• So leukocytes can squeeze through the junctions

Question 7

What sort of arteries activated endothelium do leukocytes adhere to? What happens?

Answer 7

1. adhere to activated endothelium of large arteries 2. get stuck in the subendothelial space

Question 8

Where do monocytes migrate to and what happens to them?

Answer 8

1. migrate into the subendothelial space

2. differentiate into macrophages and become foam cells

Question 9

What does the endothelium regulate?

Answer 9

flux of fluids and molecules from blood to tissues and vice versa

Question 10

Where do Atherosclerotic plaques occur?

Answer 10

preferentially at bifurcations and curvatures of the vascular tree

Question 11

Why do atheroscelrotic plaques occur there?

Answer 11

low patterns and hemodynamic forces are not uniform in the vascular system

Question 12

What is blood flow like in straight parts of the arterial tree?

Answer 12

1. blood flow is laminar

2. wall shear stress is high and directional

Question 13

What is blood flow like in branches and curvatures?

Answer 13

1. blood flow is disturbed

2. nonuniform and irregular distribution of low wall shear stress.

Question 14

What does laminar blood flow promote?

Answer 14

1. anti-thrombotic, anti-inflammatory factors
2. endothelial survival
3. Inhibition of SMC proliferation
4. Nitric oxide (NO) production

Question 15

What does disturbed blood flow promote?

Answer 15

1. Thrombosis, inflammation (leukocyte adhesion)
2. endothelial apoptosis
3. SMC proliferation
4. Loss of Nitric oxide (NO) production

Question 16

What does nitric oxide to for the cardiovascular system?

Answer 16

1. Dilates blood vessels
2. Reduces platelet activation
3. Inhibits monocyte adhesion
4. Reduces proliferation of SMC in vessel wall
5. Reduces release of superoxide radicals
6. Reduces oxidation of LDL cholesterol (major component of plaque)

Question 17

What are the mechanisms in endothelial dysfunction in the pathogenesis of atherosclerosis?

Answer 17

1. Leukocyte recruitment
2. Permeability
3. Shear stress
4. Angiogenesis

Question 18

What is angiogenesis?

Answer 18

Formation of new vessels by sprouting from existing vessels

Question 19

What is angiogenesis essential for?

Answer 19

1. Embryonic development
2. Menstrual cycle
3. Wound healing

Question 20

What does angiogenesis promote?

Answer 20

Plaque growth (BAD)

Question 21

What does therapeutic angiogenesis prevent?

Answer 21

damage post-ischemia (GOOD)

Question 22

How is permeability controlled?

Answer 22

by endothelial cell-cell junctions

Question 23

What does increased permeability to lipids contribute to?

Answer 23

early plaque formation

Question 24

How do leukocytes migrate into tissues?

Answer 24

through post-capillary venules during injury/inflammation

Question 25

What type of thrombosis is frequent in COVID-19 patients?

Answer 25

• Both venous and arterial thrombi

- Incidence unknown; variability in reports and data analysis

Question 26

What is coagulopathy?

Answer 26

increased D-Dimers, Fibrinogen

Question 27

What does coagulopathy correlate to?

Answer 27

poor prognosis (covid-19)

Question 28

What type of therapy is recommended in all hospitalised COVID-19 patients?

Answer 28

• Anti-thrombotic therapy

- Local, in situ thrombosis points to endothelial role

Question 29

What are the properties of healthy endothelium?

Answer 29

anti-thrombotic and anti-inflammatory

Question 30

What does •loss of the normal antithrombotic and anti-inflammatory functions of endothelial cells cause?

Answer 30

thrombosis with associated inflammation: thromboinflammation

Question 31

What does thromboinflammation happen?

Answer 31

sepsis, ischemia-reperfusion injury etc

Question 32

What is a theory that causes the endothelial damage secondary to SARS-CoV2?

Answer 32

-cytokine storm (leads to endothelial activation and procoagulant switch)

Question 33

What does the permeability mean?

Answer 33

-Leukocytes recruitment were leukocytes shouldn’t go
-Lipoproteins through an endothelium that should be tight
So fatty streak formation

Question 34

When does angiogenesis occur in plaques?

Answer 34

advanced atherosclerotic plaques (late)

Question 35

What can be found in COVID-19 patients?

Answer 35

circulating endothelial cells

Question 36

What is another COVID-19 endothelial cell theory?

Answer 36

-SARS-CoV2 enters endothelial cells and causes direct damage

Question 37

Does SARS-CoV2 actually bind to endothelial cells?

Answer 37

no published evidence

Question 38

Is there ACE2 expression in endothelial cells?

Answer 38

confusing evidence (on epithelial not endothelial)