CVR Vascular Endothelium - in health and disease

Question 1

layers of blood vessels (outside to inside)

Answer 1

1. tunica adventitia
2. tunica media
3. tunica intima

Question 2

what travels in the tunica adventitia?

Answer 2

vasa vasorum

nerves

Question 3

what forms the tunica media?

Answer 3

smooth muscle cells

Question 4

whatforms the tunica intima?

Answer 4

endothelium

Question 5

what vessel types are formed only by endothelial cells?

Answer 5

1. capillaries

2. venules

Question 6

which cells support the endothelial cells that make up capillaries/venules?

Answer 6

pericytes (mural cells)

Question 7

microvascular endothelium promotes what?

Answer 7

tissue homeostasis

Question 8

What is the microvascular endothelium the source of and what is their role?

Answer 8

angiocrine factors

Required for tissue homeostasis and organ regeneration

Question 9

what diseases does dysfunctional endothelium contribute to? (4)

Answer 9

• ischaemia
• chronic inflammatory diseases
• cancer
• diabetes

Question 10

what contributes to vascular and endothelial heterogeneity?

Answer 10

endothelial cells and microvasculature have organotypic (tissue specific) properties and expression profiles

Question 11

what is contact inhibition?

Answer 11

when two cells come together, causing them to stop growing

Question 12

do endothelial cells have a long life?

Answer 12

yes.

And low proliferation rate (unless new vessels required: angiogenesis)

Question 13

what is the function of endothelial cells?

Answer 13

regulate essential functions of blood vessels

Question 14

What are the essential functions of the endothelium? (5)

Answer 14

• angiogenesis
• haemostasis and thrombosis
• inflammation
• permeability
• vascular tone

Question 15

What are factors that lead to an activated endothelium (7)

Answer 15

1. mechanical stress
2. inflammation
3. viruses
4. smoking
5. high glucose
6. oxidised LDL
7. high blood pressure

Question 16

response to injury model of artherosclerosis

Answer 16

• Endothelial dysfunction results in endothelial activation
• endothelial permeability increases, leukocyte migration increases, leukocyte adhesion increases
• leads to foam cell formation
• fatty streak formation occurs
• macrophage accumulation, formation of necrotic core and angiogenesis occur - formation of an advanced, complicated lesion of atherosclerosis

Question 17

stages of leucocyte adhesion cascade during inflammation of post-capillary venules (5)

Answer 17

1. capture
2. activation
   rolling, slow rolling, arrest
3. adhesion strengthening, spreading
4. intravascular crawling
5. paracellular and transcellular transmigration

Question 18

why is the stages of leucocyte adhesion different in atherosclerosis to what happens in post-capillary venules?

Answer 18

• leukocytes are adhering to activated endothelial cells of large arteries and get stuck in the subendothelial space

Question 19

what happens to leucocytes stuck in the subendothelial space?

Answer 19

monocytes differentiate into macrophages and become foam cells

Question 20

what leaks through junctions if endothelial cell permeability increases?

Answer 20

plasma proteins

Question 21

stages of lipoprotein trapping

leading to fatty streak formation

Answer 21

1. endothelial cells are leaky
2. lipoproteins leak from vessel
3. lipoproteins get oxidised by proteoglycans
4. macrophages engulf these oxidised lipoproteins -> forming foam cells

Question 22

why does artherosclerosis occur preferentially at bifurcation and curvatures of the vascular tree?

Answer 22

• the flow patterns and haemodynamic forces are not uniform in the vascular system

Question 23

what type of blood flow occurs in the straight parts of the arterial tree?

Answer 23

laminar - wall shear stress is high and directional

Question 24

what type of blood flow occurs in the branched parts of the arterial tree?

Answer 24

turbulent flow - non uniform and irregular distribution of low wall shear stress

Question 25

what does laminar blood flow promote? (4)

Answer 25

- anti-thrombotic and anti-inflammatory factors - endothelial survival - inhibition of SMC proliferation - nitric oxide production

Question 26

What does disturbed blood flow promote?

Answer 26

Thrombosis,inflammation Endothelial apoptosis SMC proliferation Loss of Nitric oxide production

Question 27

protective effects of nitric oxide (6)

Answer 27

1. reduced oxidation of LDL cholesterol (major component of plaque) 2. reduces release of superoxide radicals 3. dilates blood vessels 4. Reduces platelet activation 5. inhibits monocyte adhesion 6. reduces proliferation of smooth muscle cells in the vessel

Question 28

what physiological processes is angiogenesis necessary for? (3)

Answer 28

1. embryonic development 2. wound healing 3. menstrual cycle

Question 29

What are two other important roles of angiogenesis?

Answer 29

Promotes plaque growth | Therapeutic angiogenesis prevents damage post- ischaemia

Question 30

stages of endothelial involvement with SARS-CoV2 infection

Answer 30

SARS-COV2 infection -> cytokine storm -> endothelial activation -> procoagulant switch (endothelium loses ability to be anticoagulant)

Question 31

types of macrophage scavenger receptors

Answer 31

A and B

Question 32

how is arterial Ox-LDL useful?

Answer 32

safe clearance, | reverse cholesterol transport

Question 33

What is the main host receptor in covid?

Answer 33

ACE2 - not on endothelial cells, but epithelial cells

Question 34

Where do the majority of endothelial cells reside?

Answer 34

capillaries

Question 35

Physiologically, in which vessels does leukocyte transmigration occur?

Answer 35

In post-capillary venules | Same as capillaries but with more pericytes

Question 36

Which processes promotes early development of atherosclerotic plaques (3)?

Answer 36

1. endothelial activation 2. permeability 3. leukocyte adhesion

Question 37

How are endothelial cells structured? (3)

Answer 37

Have a large surface area: endothelium is >1000m2 They're very flat and around 1-2 um thick and 10-20um in diameter Form a monolayer of endothelial cells which is 1 cell thick (contact inhibition)

Question 38

What are 4 things that an activated endothelium leads to?

Answer 38

Thrombosis Permeability Senescence Leukocyte recruitment

Question 39

What are risk factors and stimuli for endothelial cell dysfunction? (10)

Answer 39

``` Hypercholesterolaemia Diabetes mellitus/ metabolic syndrome Hypertension Sex hormone imbalance Aging Oxidative stress Proinflammatory cytokines Infectious agents Environmental toxins Hydrodynamic forces ```