Vascular Endothelium in Cardiovascular disease

Question 1

Where do most endothelial cells reside?

Answer 1

98% of all endothelial cells reside within the microvasculature.

Question 2

What are the 3 layers of blood vessels?

Answer 2

Tunica adventitia - Vasa vasorum ,nerves
Tunica Media - Smooth muscle cells
Tunica Intima - Endothelium

Question 3

What are capillaries made up of?

Answer 3

Endothelial cells & pericytes

Question 4

What is the role of the Microvascular Endothelium?

Answer 4

It is the source of angiocrine factors that maintain tissue homeostasis & organ regeneration.

Question 5

What diseases can dysfunctional endothelium contribute to ?

Answer 5

Ischemia
Chronic inflammatory disease
Cancer
Diabetes

Question 6

What are organotypic properties?

Answer 6

Endothelial cells have tissue specific properties & expression profiles. Heterogenous.

Question 7

How deep are endothelial cells?

Answer 7

Monolayer - 1 cell deep

Question 8

What is the role of the endothelium?

Answer 8

Barrier separating blood from tissues
Very extensive >1000m2, >100g
Very flat cells

Question 9

What is Contact inhibition?

Answer 9

Formation of endothelial cell junctions, resulting in cells saying to each other stop growing.

Question 10

What is the life span of endothelial cells?

Answer 10

Endothelial cells have a long life & low proliferation rate, unless there is damage.

Question 11

What are some essential functions of blood vessels controlled by endothelial cells?

Answer 11

Vascular tone
Aniogenesis
Haemostasis & thrombosis
Permeability
Inflammation

Question 12

What is Angiogenesis?

Answer 12

Formation of new blood vessels.

Question 13

What pathways are activated when endothelial cells are resting?

Answer 13

Anti-Inflammatory
Anti-thrombotic
Anti-proliferative

Question 14

What pathways are activated when endothelial cells are activated?

Answer 14

Pro-inflammatory
Pro thrombotic
Pro-Angiogenic

Question 15

What triggers chronic activation of the endothelium?

Answer 15

Smoking
Viruses
Mechanical stress
Inflammation
High Blood pressure
OxDl
High Glucose

Question 16

What does Chronic activation of the endothelium result in over time?

Answer 16

Thrombosis
Senescence
Permeability
Leukocyte recruitment
ALL contribute to the development of atherosclerosis.

Question 17

What is the Pathogenesis of Atherosclerosis?

Answer 17

Initial injury results in activation of the endothelium.
This causes an increase in; Endothelial permeability, systems which promote adhesion & migration of leukocytes. This results in leukocyte accumulation in sub-endothelial space. Phagocytosis of the lipids there causes Foam-cell formation.
Formation o an advanced complicated lesion of atherosclerosis.

Question 18

What does the formation of an advanced complicated lesion of Atherosclerosis consist of?

Answer 18

Macrophage accumulation
Formation of Necrotic core
Fibrous Cap formation
Angiogenesis

Question 19

What are some stimuli & risk factors for Endothelial cell dysfunction in Atherogenesis?

Answer 19

Hypercholesterolaemia
Diabetes mellitus
Hypertension
Ageing
Oxidative stress
Proinflammatory cytokines

Question 20

What allows the Leukocyte adhesion cascade?

Answer 20

Inflammatory agents activate endothelium to express molecules that support this process.

Question 21

What is the difference in structure between Capillaries & Post-capillary venules?

Answer 21

PCV have more pericytes

Question 22

When does the recruitment of blood leukocytes into tissues normally take place?

Answer 22

During inflammation;

Leukocytes adhere to the endothelium of the post-capillary venules and transmigrate into tissues.

Question 23

What is different about the recruitment of blood leukocytes in atherosclerosis?

Answer 23

Leukocytes adhere to activated endothelium of large arteries and get stuck in the sub-endothelial space

Question 24

What is the role of Monocytes in Atherosclerosis?

Answer 24

Migrate into the sub-endothelial space, differentiate into macrophages and become foam cells.

Question 25

What does increased vascular permeability lead to?

Answer 25

Leakage of plasma proteins through the junctions into the sub-endothelial space.

Question 26

How does vascular permeability lead to atherosclerosis?

Answer 26

Lipoproteins come through leaky junctions and bind proteoglycans. They get oxidated in the sub-endothelial space (good environment for oxidation). Macrophages englobate Lipoproteins to form Foam cell.

Question 27

What are the three stages in the development of Atherosclerosis?

Answer 27

1 - Endothelial cell dysfunction 2 - Fatty streak Formation 3 - Atherosclerosis lesion formation

Question 28

Where do atherosclerosis plaques preferentially occur?

Answer 28

Bifurcations and curvatures of the vascular tree

Question 29

Where is blood flow laminar?

Answer 29

Straight parts of the arterial tree. | Wall shear stress is high and directional

Question 30

Where is blood flow Disturbed?

Answer 30

Branches & Curvatures. | Non-uniform & irregular distribution of low wall shear stress.

Question 31

What does Laminar blood flow promote?

Answer 31

Anti-thrombotic, anti-inflammatory factors endothelial survival Inhibition of SMC proliferation Nitric oxide (NO) production

Question 32

What does Disturbed blood flow present?

Answer 32

Thrombosis, inflammation (leukocyte adhesion) endothelial apoptosis SMC proliferation Loss of Nitric oxide (NO) production

Question 33

Why is NO essential for the health of the Cardiovascular system?

Answer 33

``` It; Dilates blood vessels Inhibits monocyte adhesion Reduces platelet activation Reduces proliferation of SMC in the vessel wall Reduces release of superoxide radicals Reduces oxidation of LDL Cholesterol ```

Question 34

What is Angiogenesis essential for?

Answer 34

Embryonic development Menstrual cycle Wound Healing

Question 35

Why is Angiogenesis two-faced?

Answer 35

It promotes plaque growth but prevents damage post iscchaemia.

Question 36

What are circulating endothelial cells a marker of in Covid-19?

Answer 36

Severe injury, levels can be corrected by anticoagulation. Covid has been proposed as a disease of endothelial cell dysfunction

Question 37

What leads to thromboinflammation?

Answer 37

loss of the normal antithrombotic and anti-inflammatory functions of endothelial cells causes thrombosis with associated inflammation.

Question 38

What is the cascade between covid infection and Procoagulation?

Answer 38

Covid infection Cytokine storm Endothelial activation Procoagulant switch