18. Vascular Endothelium Flashcards
Define atherosclerosis
The build up of fibrous and fatty material inside the arteries
Give a symptoms atherosclerosis
chest pain (angina) leading to myocardial infarction, stroke or peripheral artery disease
What type of disease is atherosclerosis?
Chronic inflammatory disease of the arteries
What are the three layers of the blood vessels?
o Tunica Intima - ENDOTHELIUM
o Tunica Media - Smooth Muscle Cells
o Tunica Adventitia - Vasa Vasorum, Nerves
Define vasa vasorum
A network of small blood vessels that supply the walls of large blood vessels
What kind of cell layer is the endothelia?
Single layer of cells
Define contact inhibition
When the endothelial cells divide they know they have to form a monolayer
What are the critical function of endothelial cells?
1) Inflammation
2) Vascular Tone and Permeability
3) Angiogenesis
4) Thrombosis and Haemostasis
In healthy tissue what kind of state are endothelial cells in?
Anti-inflammatory and anti-thrombotic state
What happens when you have some inflammation or cut yourself?
The endothelium flips to produce a pro-inflammatory, pro-thrombotic and pro-angiogenic factors.
In atherosclerosis the endothelium receives a chronic number of stimuli
Where do leukocytes adhere to during normal inflammation?
The adhere to the endothelium of post-capillary venules and transmigrate into tissues
In atherosclerosis where do leukocytes adhere to?
They adhere to the activated endothelium of large arteries and get stuck in the subendothelial space
In terms of leukocyte migration what happens when the endothelium becomes activated?
It starts to express ligands for the leukocytes
What causes the weak interaction between the leukocyte and endothelium as well as making the leukocyte roll?
Selectins
What changes the integrins on the leukocyte to its high affinity state?
Chemokines
What does the integrin bind to?
Ligands on the endothelium
Give examples of integrins
LFA-1
VLA-4
Give examples of ligands
ICAM-1
VCAM-1
Where do leukocytes transmigrate?
The squeeze through endothelial junctions
How do the cell membrane proteins on each endothelial cell bind?
Homophilic way
How are the endothelial junctions arranged?
The junctions act as zippers which can allow things to pass through without the endothelium falling apart
What is reason why atherosclerosis only occurs in arteries?
If leukocytes adheres to an artery it can go through the endothelium but go no further.
What is below the endothelium?
Layer of sticky molecules (collagen and proteoglycan)
Where does atherosclerosis tend to form?
At branch points where you get turbulent flow
What does laminar blood flow promote?
o Nitric oxide production
o Factors that inhibit coagulation, leukocyte adhesion, smooth muscle cell proliferation
o Endothelial survival
What does turbulent blood flow promote?
o Coagulation, leukocyte adhesion, smooth muscle cell proliferation
o Endothelial apoptosis
Define angiogenesis
The formation of new blood vessels by sprouting from pre-existing vessels
What is angiogenesis controlled by?
Endothelial cells
What happens when the tissue is hypoxic?
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
How can angiogenesis be both a positive and negative thing?
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.
How does angiogenesis promote the growth of atherosclerotic plaques?
With advanced plaques they cause hypoxia due to large amounts of necrotic debris. They hypoxia stimulates angiogenesis from the vasa vasorum
Define senescence
growth arrest that halts the proliferation of ageing and/or damaged cells
What is negative thing about senescence?
Senescent cells can develop a proinflammatory phenotype
What contributes to atherosclerotic plaque progression?
Senescent cells because they have a pro-inflammatory and pro-thrombotic phenotype
How can endothelial senescence be induced?
By cardiovascular risk factors such as oxidative stress
What is the overview of atherosclerosis?
- 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
