Atherosclerosis Flashcards
3 Stages of Arteriosclerosis
Endothelial Damage
Uptake of modified LDL particles
Adhesion + infiltration of macrophages
Smooth muscle proliferation + formation of fibrous cap
Vasodilators
NO
PGI2
Vasoconstrictors
Angiotensin II
Endothelin
Fibrinolysis
Process that prevents blood clots
Endothelium dysfunction
Imbalance between vasodilating + vasoconstricting substances
Endothelium Damage causes
Shear stress Toxic damage High lipid levels Viral/bacterial infection Dysfunctional damaged endothelium
Lipoproteins
Lower the density of a lipoprotein, the more lipid it contains relative to protein
Lowest to highest density lipoprotein
Chylomicron –> VLDL –> IDL –> LDL –> HDL
Chylomicron Main component + Apoprotein
TG
B48 (A,C,E)
VLDL Main component + Apoprotein
TG
B100 (A,C,E)
IDL Main component + Apoprotein
TG + cholesterol
B100, E
LDL Main component + Apoprotein
Cholesterol
B100
HDL Main component + Apoprotein
Protein
AI, AII (C,E)
Biggest Lipoprotein –> smallest
Chylomicron –> VLDL –> IDL –> LDL –>HDL
Oxidation of LDLs
Facilitated by reactive O2 species (free radicals)
Decreased by antioxidants in fruit + veg
Stimulates expression of inflammatory mediators including adhesion molecules
Glycation of LDLs
High glucose levels
Higher glycated LDLs in diabetes
Glycated LDL more likely to get oxidised
Infiltration of macrophages
Endothelial Damage/oxidised LDLs –> attract monocytes
Monocytes bound to/cross endothelium
Transformed into macrophages –> accumulate oxidised LDLs
Fat-laden foam cells appear as fatty streaks
Normal LDL uptake
LDL receptor recognises B100
Internal accumulation of LDL by macrophages
Lower LDL surface receptors –> lower uptake
Modified LDL uptake
Modified LDL not recognised by LDL receptor
Instead taken up via scavenger receptor
NO negative feedback
LDL accumulates in large droplets- FOAM CELLS
Fibrous cap formation
Damage to Endothelium LDL oxidation + entry Taken up by macrophages Lipid filled foam cells Create subendothelial pool Cytokines secreted by endothelium + macrophages stimulates migration of SMC Secrete collagen forming a fibrous cap Rupture can lead to thrombus formation
Stable Plaque
Slow growing
Fibrin cap matures (not prone to rupture)
Reduced blood flow
Stable angina (exertional)
Unstable Plaque
Grow quickly - rapid lipid deposition Thin fibrin cap Fragile cap ruptures Thrombus formation Reduced lumen diameter May occlude lumen completely (MI)
Fragile cap rupture
Haemorrhage from plaque
Release of platelet tissue factor (clotting cascade)
Collagen exposed causing platelet aggregation
Total cholesterol adult
under 200mg/dl
LDL adult
Under 130 mg/dl
HDL adult
over 40mg/dl
triglyceride range
10-190 mg/dl
Homocystinaemia
RF for unstable plaque
Increased homocysteine (B6, B12 + folic acid deficiencies)
Increase oxidant stress
Need to up B vitamin intake to combat
B vitamin uptake pathway
Methionine –> homocysteine in bloodstream
Homocysteine –> cysteine (B6) (cell folding/antioxidant)
Homocysteine –> back to methionine (B12)
Lipoprotein (a)- LDL + extra apolipoprotein
RF for unstable plaque
More firmly retained in arterial wall
Infection
Unstable plaque RF
Chlamydia pneumoniae
inflammation of endothelium
Treatment Unstable Plaques
Modifiable risk factors
Statins
Polypill
Statins MOA
Inhibit HMG CoA Decrease cholesterol in liver cells increase uptake from circulating blood plasma increase LDL receptors decrease plasma cholesterol
Polypill
More than 80% CV disease reduction Statin x 3 BP lowering drugs (thiazide, B blocker, ACE inhibitor) B vitamins Aspirin
Atherosclerosis Complications
Coronary Artery disease (Angina, MI) Peripheral vascular disease (ulcers) Stroke aneurysm renal artery stenosis
Stent
Maintains patency of blood vessel
