Atheroscleorosis Flashcards
(32 cards)
What are the three stages of development of atherosclerosis?
1) Endothelial damage
2) Uptake of modified LDL particles and adhesion and infilitration of macrophages
3) Smooth muscle proliferation
Name 3 functions of the endothelium
1) Maintaining vasomotor tone
2) Regulation of thrombosis- provides receptors for procoagulatants and anticoagulants. Usually the latter
3) Inflammatory factors
What is main vasodilator/ vasoconstrictor in endothlium?
Vasodilator= NO/ PG12 Vasconstriction= Angiotensin and endothelin
Name 4 ways that the endothelium can be damaged
1) Shear stress
2) Infection
3) Toxic damage
4) Hyperlipedemia
What is meant by shear stress?
Turbulent flow causing damage
Usually in medium/ large branching arteries
Describe make up of chylomicron
50% protein and 50% fat
Role of VLDL
Where is it synthesised?
Carries fat from the liver to cells
Synthesised in the liver
Role of IDL
Breaks down product of VLDL
Role of LDL
Transports fat from cells to blood vessels
BAD
Role of HDL
Transports fat from blood vessel to liver
GOOD
The lower the density of lipoprotein….
MOre lipid it contains relative to protein
How does damage to the endothelium change the way lipoproteins are uptaken?
LDLs can become trapped in subendothelial space when there is substantial damage
What happens when one lipoprotein is trapped
Attracts more and undergoes oxidation
What facilitates oxidation of trapped lipoproteins
Free radicals
When is glycation of trapped lipoproteins more likely
Patients with diabetes
HIgher circulating glucose means glycated LDL
Is glycated LDL more or less likely to be oxidised
More
How does oxidation of lipoproteins lead to monocyte adhesion
Oxidised LDL stimulates expression of inflammatory mediators
Adhesion molecules of monocytes
What happens to monocytes when they move into subendothelial space
Transformed into macrophages
How do macrophages behave in subendothelial space
Try to absorb LDLs and accumulate forming foam cells/ fatty streaks
Describe normal regulation of LDL uptake
LDL-receptor mediated endocytosis
Receptor recognises apolipoprotein B100
B100 is allowed into the cell
Negative feedback occurs as internal accumulation of LDL reduces the number of LDL surface receptors
How is regulation of LDL uptake different when LDL are modified
Not recognised by LDL receptors
Uptaken by scavenger receptor
No negative feedback- uncontrolled
What happens to fatty streak?
Matures into a plaque
How do endothelial cells respond to a plaque?
Endothelial cells and macrophages release growth factors that cause proliferation of smooth muscle in intima
This leads to collagen production and atrophy of internal elastic lamina
How does the body try to contain the plaque
With a collagen fibrous plaque
