17 Atherosclerosis Flashcards
Q: What are the inflammatory cells that come into atherosclerotic plaques?
A: Macrophages
Q: How does the function of smooth muscle and macrophages vary in atherosclerotic plaques? (3)
A: Smooth muscle cells and macrophages have contrasting functions
Macrophages are there to remove arterial tissue
smooth muscle cells are there to make more arterial tissue
Smooth muscle cells protect plaque integrity, they make more tissue which strengthens the artery
Q: Which diseases are associated with atherosclerosis? (2) How has their occurrence changed?
A: ischaemic heart disease and cerebrovascular disease
have increased in the world disease burden ranking
Q: What are the potentially modifiable risk factors for atherosclerosis? (6) Not modifiable? (3) If you have two or three different risk factors then the risk associated is?
A: Smoking Lipids Blood Pressure Diabetes Obesity Lack of Exercise
Age
Sex
Genetic Background
MULTIPLICATED
Q: Describe the distribution of atherosclerosis in the body?
A: Atherosclerosis is NOT evenly distributed - it tends to arise at specific places such as the bifurcation of the common carotid artery
Q: In terms of bends in blood vessels. Where do athersclerotic lesions tend to appear? why? (3) how?
A: Blood flow in arteries is LAMINAR so the blood flows fastest in the middle of the vessel and slower around the outside
When the blood goes around a corner too quickly it sets up EDDYs (turbulent flow)
Therefore, atherosclerotic lesions tend to appear on the outside of a bend rather than on the inside
Q: How does atherosclerosis form and progress? (7)
A: 1. LDLs deposit in the SUBINTIMAL SPACE and binds to matrix proteoglycans (when LDL are too high- exceed regulated endocytotic capacity of endothelium cells)
- > Once the LDLs enter the subintimal layer, a chain reaction is established (oxygen free radicals attack LDLs)
2. lesion begins small and then LDLs accumulate which brings in macrophages
3. macrophages eat up the endothelial fat (take in oxidised LDLs) via scavenger receptors and become FOAM CELLS and remove themselves from the viscinity: macrophages are capable of removing fat from the artery wall - reverse cholesterol transport
(macrophages also release oxygen free radicals)
- The macrophages and endothelial cells produce growth factors that stimulate smooth muscle cells to grow, divide
Macrophages also secrete matrix metalloproteinases which degrade collagen in the artery wall
- smooth muscle cells make collagen = forms fibrous cap (SM cells may also accumulate lipids and form foam cell)
The inflammation (stimulated by T cells recruited by macrophages) irritates the interior of the plaque to form a fibrous thickening
- As fat deposition continues, the lesion accumulates pools of extracellular lipids (outside the macrophages) and the macrophages can no longer cope
- macrophages are overwhelmed by the intracellular fat so die by apoptosis and release the toxic lipids and macrophage tissue factor into the necrotic core -> soft core of extracellular lipids and necrotic macro.
Q: What will eventually occur to an atherosclerotic plaque? result? Describe the layering effect. (4)
A: Eventually the plaque will RUPTURE which allows the lipid core (which is thrombogenic) to communicate with the lumen and stimulate clot formation within the lumen
comes from repeat episodes of plaque destabilisation
small episodes of thrombus forming and then stopping
the thrombi form one after another
to narrow the lumen a little bit at a time
Q: Name the 5 cell types involved in the development of an atherosclerotic plaque.
A: Vascular endothelial cells
Platelets
Monocyte-macrophages
Vascular smooth muscle cells
T lymphocytes
Q: What’s the role of vascular endothelial cells in the development of an atherosclerotic plaque? (2)
A: Barrier function (eg to lipoproteins)
Leukocyte recruitment
Q: What’s the role of platelets in the development of an atherosclerotic plaque? (2)
A: Thrombus generation
Cytokine and growth factor release
Q: What’s the role of monocytes-macrophages in the development of an atherosclerotic plaque? (4) What do these cells become due to the abnormal inflammatory action in advancing lesions?
A: Foam cell formation
Cytokine and growth factor release
Major source of free radicals
Metalloproteinases= group of enzymes that are responsible for the degradation of most extracellular matrix proteins inc collagen
become an inappropriate source of free radicals
Q: What’s the role of vascular smooth muscle cells in the development of an atherosclerotic plaque? (3) What do these cells do in an abnormal artery with an atherosclerotic plaque?
A: Migration and proliferation
Collagen synthesis
Remodelling and fibrous cap formation
can synthesise and secrete COLLAGEN which contributes to the stabilisation of the plaque and fibrous cap
Q: What’s the role of T lymphocytes in the development of an atherosclerotic plaque?
A: Macrophage activation: T cells - the feedback of macrophages activates T cell and the activated T cells, in turn, activate macrophages
Q: What are the 2 systems responsible for haemostasis? What can they generate? (2)
A: Clotting Cascade
Platelet Aggregation
Platelet aggregation and the coagulation cascade generate normal clotting but they can also generate abnormal clotting (thrombosis)
Q: What are foam cells? Size? What happens to foam cells over time? End result?
A: (can be vascular smooth muscle cells)
Macrophages phagocytose modified lipoproteins when they enter the subendothelial layer
they start off small but as they get further and further in they get bigger and bigger
These foam cells end up getting very sick because they are bloated with fat
They become so bloated with fat that the fat comes out of solution forming fat globules within the macrophage which eventually kills it
Q: Which cells are a key source of free radicals? What is the role of FRs?
A: macrophages
immune system makes as part of the natural immune function to kill microbes
