18. Vascular Endothelium

Question 1

Define atherosclerosis

Answer 1

The build up of fibrous and fatty material inside the arteries

Question 2

Give a symptoms atherosclerosis

Answer 2

chest pain (angina) leading to myocardial infarction, stroke or peripheral artery disease

Question 3

What type of disease is atherosclerosis?

Answer 3

Chronic inflammatory disease of the arteries

Question 4

What are the three layers of the blood vessels?

Answer 4

o Tunica Intima - ENDOTHELIUM
o Tunica Media - Smooth Muscle Cells
o Tunica Adventitia - Vasa Vasorum, Nerves

Question 5

Define vasa vasorum

Answer 5

A network of small blood vessels that supply the walls of large blood vessels

Question 6

What kind of cell layer is the endothelia?

Answer 6

Single layer of cells

Question 7

Define contact inhibition

Answer 7

When the endothelial cells divide they know they have to form a monolayer

Question 8

What are the critical function of endothelial cells?

Answer 8

1) Inflammation
2) Vascular Tone and Permeability
3) Angiogenesis
4) Thrombosis and Haemostasis

Question 9

In healthy tissue what kind of state are endothelial cells in?

Answer 9

Anti-inflammatory and anti-thrombotic state

Question 10

What happens when you have some inflammation or cut yourself?

Answer 10

The endothelium flips to produce a pro-inflammatory, pro-thrombotic and pro-angiogenic factors.
In atherosclerosis the endothelium receives a chronic number of stimuli

Question 11

Where do leukocytes adhere to during normal inflammation?

Answer 11

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

Question 12

In atherosclerosis where do leukocytes adhere to?

Answer 12

They adhere to the activated endothelium of large arteries and get stuck in the subendothelial space

Question 13

In terms of leukocyte migration what happens when the endothelium becomes activated?

Answer 13

It starts to express ligands for the leukocytes

Question 14

What causes the weak interaction between the leukocyte and endothelium as well as making the leukocyte roll?

Answer 14

Selectins

Question 15

What changes the integrins on the leukocyte to its high affinity state?

Answer 15

Chemokines

Question 16

What does the integrin bind to?

Answer 16

Ligands on the endothelium

Question 17

Give examples of integrins

Answer 17

LFA-1

VLA-4

Question 18

Give examples of ligands

Answer 18

ICAM-1

VCAM-1

Question 19

Where do leukocytes transmigrate?

Answer 19

The squeeze through endothelial junctions

Question 20

How do the cell membrane proteins on each endothelial cell bind?

Answer 20

Homophilic way

Question 21

How are the endothelial junctions arranged?

Answer 21

The junctions act as zippers which can allow things to pass through without the endothelium falling apart

Question 22

What is reason why atherosclerosis only occurs in arteries?

Answer 22

If leukocytes adheres to an artery it can go through the endothelium but go no further.

Question 23

What is below the endothelium?

Answer 23

Layer of sticky molecules (collagen and proteoglycan)

Question 24

Where does atherosclerosis tend to form?

Answer 24

At branch points where you get turbulent flow

Question 25

What does laminar blood flow promote?

Answer 25

o Nitric oxide production
o Factors that inhibit coagulation, leukocyte adhesion, smooth muscle cell proliferation
o Endothelial survival

Question 26

What does turbulent blood flow promote?

Answer 26

o Coagulation, leukocyte adhesion, smooth muscle cell proliferation
o Endothelial apoptosis

Question 27

Define angiogenesis

Answer 27

The formation of new blood vessels by sprouting from pre-existing vessels

Question 28

What is angiogenesis controlled by?

Answer 28

Endothelial cells

Question 29

What happens when the tissue is hypoxic?

Answer 29

The tissue will release chemicals which triggers a change in the cells. The cells that become a tip cell takes over and controls the formation of the blood vessel

Question 30

How can angiogenesis be both a positive and negative thing?

Answer 30

Negative - It promotes the growth of atherosclerotic plaques
Positive - therapeutic angiogenesis can be used to prevent tissue damage and hence prevent heart failure after an acute myocardial infarction to reoxygenate the myocardium down stream of the occlusion.

Question 31

How does angiogenesis promote the growth of atherosclerotic plaques?

Answer 31

With advanced plaques they cause hypoxia due to large amounts of necrotic debris. They hypoxia stimulates angiogenesis from the vasa vasorum

Question 32

Define senescence

Answer 32

growth arrest that halts the proliferation of ageing and/or damaged cells

Question 33

What is negative thing about senescence?

Answer 33

Senescent cells can develop a proinflammatory phenotype

Question 34

What contributes to atherosclerotic plaque progression?

Answer 34

Senescent cells because they have a pro-inflammatory and pro-thrombotic phenotype

Question 35

How can endothelial senescence be induced?

Answer 35

By cardiovascular risk factors such as oxidative stress

Question 36

What is the overview of atherosclerosis?

Answer 36

• At the beginning you have risk factors which activate the endothelium and promotes permeability, leukocyte adhesion and leukocyte migration
• Leukocytes which enter the subendothelial layer begin to phagocytose LDLs and form foam cells producing fatty streaks
• After a long time, this becomes a large complex plaque with angiogenesis and senescence possible playing a role