8 - Atherosclerosis Flashcards
Arteriosclerosis
Thickening of arterial wall which then loses elasticity
3 steps in development of atherosclerosis
1 - Endothelial damage
2 - Uptake of modified LDL particles, adhesion and infiltration of macrophages
3 - Smooth muscle proliferation and formation of fibrous cap
4 endothelial functions
Vasomotor tone
Thrombosis
Inflammatory factors
Cellular adhesion molecules
Causes of endothelial damage
Shear stress
toxic damage
high LDL levels
Viral/bacteria
VLDL
Very low density lipoprotein
Liver to cells
B100, A,C,E
Chylomicron
Largest lipoprotein
B48, A,C,E
IDL
Intermediate density lipoprotein
Breakdown product of VLDL
B100, E
LDL
Low density lipoprotein
Fat from cell to blood vessel
B100
HDL
High density lipoprotein
Removes fat from blood vessel to liver
A1, AII, C,E
What facilitates and decreases oxidisation of LDLs
Reactive oxygen species in pollutants/nicotine facilitate
Antioxidants in fruit and veg decrease
What facilitates glycation
High glucose levels
glycated LDL more likely to be oxidised
How are monocytes transformed to fatty streaks
Monocytes cross the endothelium and are transformed into macrophages
They accumulate large droplets of lipid to become foam cells
this then becomes a fatty streak
What receptor is modified LDL uptaken by
Scavenger receptor
Where does smooth muscle proliferation take place
Intima
What is the role of PDGF
Growth factor released by endothelial cells and macrophages
Causes proliferation of SMC
Also chemoattractant
Stable plaque
Reduces blood flow, slow growing, increasing plaque volume causes stenosis of lumen and limits flow (stable angina) no thrombus
Unstable plaque
Unstable fibrous plaque, can rupture and haemorrhage - release of platelet TF - clotting cascade- collagen exposed causing platelet aggregation
Forms a thrombus which may cause a Mi
Desirable total cholesterol
Under 200mg/dl
Desirable LDL
Under 130 mg/dl
Desirable HDL
over 40mg/dl
Desirable triglycerides
10-190mg/dl
Atherosclerosis risk factors
Age, Sex, family history
Smoking, hypertension, diabetes, physical activity
Homocystinaemia, infection
What do statins do
Inhibit HMG CoA to decrease cholesterol in liver cells, increase LDL receptors and decrease plasma cholesterol
Complications of atherosclerosis
Coronary Artery Disease
Stroke
Aneurysm
Renal artery stenosis
What do LDL receptors recognise
Apoplipoprotein B100
What usually occurs in LDL uptake
Negative feedback - accumulation of LDL, decrease in LDL receptors and decrease in LDL uptake
What occurs in atherosclerosis in LDL uptake
Modified LDL are not recognised by LDL-receptor
modified LDL uptake by scavenger receptor
UNLIMITED UPTAKE
LDL accumulates in large droplets (foam cells)
What causes fatty streak to turn into a mature plaque
Endothelial cells + macrophages release growth factors such as PDGF
Proliferation of SMCs in intima + collagen production
Breakdown of internal elastic lamina
SMC –> foam cells
Collagen forms fibrous cap
What is the polypill
Statin
Folic acid
3bp lowering drugs to reduce LDL + bp
