Atherosclerosis Flashcards
what is Atherosclerosis?
Narrowing and hardening of medium and large arteries, reducing blood flow
ED dysfunction = fatty streaks
increased permeability = entry of LDL into intima. LDL is trapped and oxidises to become mLDL
mLDL recruit leukocytes expressing high levels of pro-inflammatory cytokines
macrophages imbibe lipoproteins to form foam cells. cellular debris causes inflammation, driving plaque formation
a cap is formed over the plaque to wall off from blood
Atherosclerosis aetiology - Endothelial dysfunction
Protective glycocalyx layer disturbed due to inflammation, oxidative stress, oxidised LDL’s, hyperglycaemia, endotoxaemia, abnormal shear stress.
Migration of phagocytic and inflammatory immune cells into blood vessels.
Disturbs NO metabolism, raises hypertension risk, increases shear stress worsening ED dysfunction leading to plaque formation.
Atherosclerosis aetiology - Inflammation
ED dysfunction, cholesterol accumulation and monocyte/T cell recruitment drives inflammatory response
Monocytes form ‘inflammasomes’ in sub-endothelial space, releasing inflammatory cytokines which activate IL-6 and CRP production enhancing inflammatory cascade in vessel walls.
Inflammation thins fibrous plaque cap leading to instability and rupture
Pro inflammatory cytokines differentiate VSMC into osteoblast like cells, increasing plaque calcification
Atherosclerosis aetiology - Dyslipidaemia
Lipids are fundamental component of atherosclerotic plaques, thus dislipidaemia is a significant risk factor
High Trigycerides (TGs). TG are hydrophobic and travel in plasma via lipoproteins. TG rich lipoproteins are prone to endothelial accumulation and uptake by foam cells.
High TGs are linked with low HDLs.
Natural approach to Atherosclerosis - promoting a healthy lipid profile
Avoid high sat fats
Increase Omega 3s and MUFAs, ie: avocado, unrefined olive oil
EVOO polyphenols (oloecanthal and oleacein) have antioxidant and anti-inflammatory effects.
Red yeast rice is a natural statin, containing monacolin K (inhibits cholesterol synthesis via HMG CoA reductase).
Increase dietary fibre: soluble fibre (veg, psyllium husks, pectin)
Include dietary sources of beta glucans (oats, mushrooms, barley)
Beta glucans also a source of SCFA - decrease liver cholesterol synthesis and increase bile excretion and modulate immune function
Natural approach to Atherosclerosis - supporting endothelial health and vasodilation
Hawthorn berries, bilberry, blueberries and blackcurrant are anti oxidants that support blood vessel integrity
Lower ET-1 levels: citrus flavonoids, quercitin, epicatechins, garlic, olive oil, ginkgo, folate, blackcurrant
Beetroot : organic nitrates convert to NO in body. Lowers homocysteine - contains betaine that remethylates homocysteine to methionine
L-theanine, increases NO production in ED cells through eNOS phosphorylation (green tea)
Reduce homocysteine - B6, folate, B12, TMG
Lower fibrinogen levels: high fibrinogen promotes atherosclerosis by increasing blood viscosity, stimulating fibrin formation and increasing platelet formation
Med. style diet for healthy levels of fibrinogen
Natural approach to Atherosclerosis - promoting and supporting liver detoxification
Ensure availability of substrates required for detox pathways (previous lecture)
Circulation of inflammatory mediators increase through poor liver function. also impedes cholesterol metabolism and compromises EFA s.
Schisandra fruit: activates phase I detox without increasing harmful substances (antioxidant and hepatoprotective effects). Enhances phase II.
Natural approach to Atherosclerosis - Nutrients and dosages
L-citrulline 500 - 3000mg/day
Panthothenic acid (active form of B5) 300mg x 3/day
Niacin (B3) 500 - 3000mg/day
Omega 3
3000 - 5000 mg/day
Pomegranate
250ml juice per day, or 2 cups seeds
Pycogenol (pine bark extract)
100 - 200mg /day
Lycopene
25mg/day
Citrus Bergamia
500 - 1000 mg/day
Globe artichoke
Dietary and 1-2g /day (powdered)
L-citrulline functions in atherosclerosis
NO sythesised from L-argeninie by eNOS.
Enhance arginine and NO bioavailability. Arginase lowers availability or oral L-arginine supplementation. L-citrulline not affected by arginase as it skips first pass metabolism before conversion to arginine.
Renal arginine regulates BP, blocks formation of enthothelin, potent antioxidant.
Panthothenic acid (B5) functions in atherosclerosis
Reduces TC, LDL, Apo-B, TGand increases HDL over 4 months, peaks at 6.
Reduces lipid disposition, oxidation and fatty streak formation. Lowers lipids in diabetics
Niacin (B3) functions in atherosclerosis
Reduces TC, LDL, Apo-B, LDL-P, TGs and VLDL
Decreases fibrinogen.
Omega 3 functions in atherosclerosis
Reduces TG, VLDL, LDL-P and chylomicron remnants. Reduces Lp-PLA2
Anti inflammatory, anti-thrombotic, lowers BP, heart rate and IR.
Reduces CVD progression and stabilises plaques
Pomegranate functions in atherosclerosis
Improves HDL function, increases reverse cholesterol transport
Potent antioxidant, lowers oxLDL and macrophage LDL uptake.
Decreases progress of carotid artery IMT
Reduces BP
Pycogenol (pine bark extract) functions in atherosclerosis
Flavonoid, antioxidant, anti -inflmmatory, anti-thrombotic
Enhances NO and ED function, reduces BP and Hs-CRP
Reduces foam cell formation
Lycopene fuctions in atherosclerosis
Anti-oxidant. Suppresses intestinal cholesterol absorption. Lowers TC, LDL-C, inflammation and increases HDL-C.
Activates PPAR-y
