17 - Atherosclerosis Flashcards
What is the end result of atherosclerosis?
ischaemic heart disease and cerebrovascular disease
Give some modifiable and non-modifiable risk factors for atherosclerosis
MODIFIABLE: - smoking - lipids - blood pressure - diabetes - obesity - lack of exercise NON-MODIFIABLE - age - sex - genetic background
NOTE: multiple risk factors give a multiplicated risk association
What has changed inn recent years that now means that atherosclerosis now treatable?
- can reduce hyperlipidemia (statins)
- can reduce hypertension (anytihypertensives)
Where does atherosclerosis tend to arise? Why?
At the bifurcation of the common carotid artery, on the outside of the bend. This is because when blood goes round a corner too quickly, it may have some turbulent flow
Give the mechanism of atherosclerosis
- LDLs enter the subintimal space and bind to matrix proteins (this causes a chronic inflammatory cascade)
- accumulation of LDLs brings in macrophages
- macrophages consume the fat cells and become FOAM CELLS
- as fat deposition occurs, the lesion accumulates pools of extracellular lipids
- the fat builds up and you get a core of extracellular lipid - the pools of fat coalesce and forms a large mass of fat
- the inflammation irritates the interior of the plaque to form a fibrous thickening
- macrophages produce growth factors, that stimulate smooth muscle cells to grow, divide and make more collagen
- eventually the plaque will rupture (this allows the lipid core to communicate with the lumen and stimulate clot formation)
What happens to the size of the lumen of arteries with age?
remains the same since the arteries expand as material accumulates
What are the 2 systems that are responsible for haemostasis?
the clotting cascade and platelet aggregation
What are foam cells?
macrophages that have consumed fat
What is the role of macrophages in atherosclerosis?
secrete cytokines and growth factors
a key source of free radicals
main inflammatory cells in atherosclerosis
What are matrix metalloproteinases?
degrade major extracellular proteins such as collagen
What are LDLs? Where are they synthesised? What is their role? What is their structure?
‘bad cholesterol’
synthesised in the liver
function: they carry cholesterol from the peripheral tissues to the rest of the body (this includes the arteries)
structure: have a lipid monolayer on their surface, with cholesterol embedded. Have apoproteins on their surface, which tell it where to go/
What are HDLs? What is their role?
‘good cholesterol’
function: carry cholesterol from the peripheral tissues (including the arteries) back to the liver
i. e. reverse cholesterol transport
What causes oxidised/modified LDLs?
What are they?
the action of free radicals
oxidised/modified LDLs are families of high inflammatory and toxic forms of LDL found in vessel walls
What traps LDL inside the subendothelial layer?
proteoglycans
How are LDLs converted into oxidised LDLs?
What happens to them after this?
- they become trapped int he subendothelial layer by proteoglycans
- attacked by free radicals, which oxidise them
- these are then phagocytosed by macrophages to form foam cells - this stimulates chronic inflammation
