Vascular Endothelium

Question 1

Blood vessels are lined by which cells?

Answer 1

Endothelial cells

Question 2

What are the three layers of blood vessels (apart from capillaries and venules)?

Answer 2

Question 3

What percentage of endothelial cells reside within the microvasculature?

Answer 3

98%

Question 4

Describe the structure of capillaries and venules

Answer 4

Formed only by endothelium
Supported by some mural cells (pericytes) and a basement membrane

Question 5

Where does exchange of nutrients and oxygen between blood and tissues occur?

Answer 5

Capillaries

Question 6

What findings suggest that microvascular endothelium promotes tissue homeostasis?

Answer 6

Damage to the endothelium can cause organ dysfunction

Question 7

Are blood vessels just a distribution system?

Answer 7

No

Question 8

Microvascular endothelium are the source of what factors and what are these factors required for?

Answer 8

Source of angiocrine factors
Factors are required for maintenance of tissue homeostasis and organ regeneration

Question 9

Dysfunctional endothelium contributes to which conditions?

Answer 9

Contributes to disease more than any other organ:
Ischaemia
Chronic inflammatory diseases
Cancer
Diabetes

Question 10

Are all blood vessels the same?

Answer 10

No, there is vascular and endothelial heterogeneity
Endothelial cells and microvasculature have organotypic (tissue-specific) properties and expression profiles

Question 11

Describe the structure of endothelial cells

Answer 11

Very flat
1-2 micrometers thick and 10-20 micrometers in diameter

Question 12

How do endothelial cells grow to from the endothelium?

Answer 12

Endothelial cells come together to form cell-cell junctions
Establishment of the junction (contains a lot of complex molecular structures) results in growth inhibition - cells stop growing
This is known as contact inhibition

Question 13

Describe the proliferation rate of endothelial cells

Answer 13

Low
Only proliferate during angiogenesis, where new vessels are required

Question 14

What is the function of endothelial cells?

Answer 14

Regulate essential functions of blood vessels:
Vascular tone
Angiogenesis
Permeability
Inflammation
Homeostasis and thrombosis

Question 15

At rest, what kind of factors are produced by the vascular endothelium?

Answer 15

Anti-inflammatory
Anti-thrombotic
Anti-proliferative

Question 16

When activated, what kind of factors are produced by the vascular endothelium?

Answer 16

Pro-inflammatory
Pro-thrombotic
Pro-angiogenic

Question 17

What factors may contribute to chronic activation of the endothelium?

Answer 17

Smoking
Viruses
Mechanical stress
Inflammation
High BP
OxLDL
High glucose

Question 18

Over time, what does chronic activation of the endothelium promote and what do these factors lead to?

Answer 18

Thrombosis
Leukocyte recruitment
Increased permeability
Ageing of endothelial cells (senescence)
Lead to atherosclerosis

Question 19

What stimuli and risk factors are implicated in endothelial cell dysfunction in atherogenesis?

Answer 19

Question 20

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

Answer 20

Leukocyte recruitment
Permeability
Shear stress
Angiogenesis

Question 21

Describe the leukocyte adhesion cascade

Answer 21

Question 22

In physiology, when does leukocyte recruitment occur and where?

Answer 22

Takes places during inflammation
Leukocytes adhere to endothelium of post-capillary venules and transmigrate into tissues

Question 23

What is the difference between a capillary and a post-capillary venule?

Answer 23

Structure similar but venules have more pericytes

Question 24

How is leukocyte recruitment different in atherosclerosis?

Answer 24

Leukocytes adhere to activated endothelium of large arteries and get struck in subendothlial space
Monocytes migrate into subendothelial space -> differentiate into macrophages -> become foam cells (following phagocytosis)

Question 25

How does vascular permeability contribute to atherogenesis?

Answer 25

Increased permeability results in leakage of plasma proteins through junctions into the subendothelial space Lipoprotein trapping (by proteoglycans, ECM) and oxidation Macrophages phagocytose material -> formation of foam cells

Question 26

Where does atherosclerosis typically occur and why?

Answer 26

Branch points - bifurcations and curvatures of the vascular tree Flow pattern and haemodynamic forces are not uniform in the vascular system - turbulent vs laminar flow

Question 27

Describe blood flow and shear stress in ‘straight’ parts of the arterial tree

Answer 27

Laminar blood flow Wall shear stress is high and directional

Question 28

Describe blood flow and shear stress in the branches and curvatures of the arterial tree. What can this cause?

Answer 28

Disturbed/turbulent blood flow Non-uniform/irregular distribution of low wall shear stress Can cause chronic endothelial activation

Question 29

Describe the protective effect of laminar blood flow on the vascular endothelium?

Answer 29

Promotes -Antithrombotic and anti-inflammatory factors -Endothelial survival -Inhibition of smooth muscle cell proliferation -Nitric oxide production Disturbed blood flow promotes the exact opposite

Question 30

Outline the protective effects of NO on the vascular endothelium

Answer 30

Essential for health of CVS - Dilates blood vessels - Reduces platelet activation - Inhibits monocyte adhesions - Reduces proliferation of SMC in vessel wall - Reduces release of superoxide radicals - Reduces oxidation of LDL cholesterol (major plaque component)

Question 31

Define angiogenesis

Answer 31

Formation of new vessels by sprouting from existing vessels

Question 32

Angiogenesis is essential for what physiological processes?

Answer 32

Embryonic development Menstrual cycle Wound healing

Question 33

Describe the JANUS paradox of angiogenesis and cardiovascular disease

Answer 33

Angiogenesis promotes plaque growth in advanced atherosclerosis However, therapeutic angiogenesis prevents damage post-ischaemia (e.g. MI)

Question 34

Describe the pathogenesis of atherosclerosis using the response to injury model

Answer 34

1. Endothelial dysfunction - Endothlial permeability - Leukocyte migration - Leukocyte adhesion 2. Fatty-streak formation - Foam-cell formation 3. Formation of an advanced, complicated lesion - Macrophage accumulation - Formation of a necrotic core - Angiogenesis

Question 35

What processes promote early development of atherosclerotic plaques?

Answer 35

Endothelial activation Leukocyte adhesion Increased permeability to lipids

Question 36

What is thromboinflammation caused by and which recent disease is it thought to be associated with?

Answer 36

Loss of normal antithrombotic and anti-inflammatory functions of endothelial cells - leads to thrombosis and associated inflammation Occurs in many disorders - thought to occur in COVID 19

Question 37

Describe two possible mechanism of endothelial activation and damage in COVID-19

Answer 37

1. COVID Infection -> cytokine storm -> endothelial activation -> procoagulant switch 2. Virus enters endothelial cells and causes direct damage (ACE2 expressed in EC?)