Atherogenesis Flashcards
Define arteriosclerosis
hardening of the arteries
generic term reflecting arterial wall thickening and loss of elasticity
Name the 3 general patterns of arteriosclerosis
arteriolosclerosis
Monckeberg medial sclerosis
atherosclerosis
Describe arteriolosclerosis
small arteries and arterioles
downstream ischaemic injury
anatomic variants, hyaline and hyperplastic
associated with diabetes and hypertension
Describe Monckeberg medial sclerosis
generally patients >50
calcific deposits (does not occlude artery lumen)
may undergo metaplastic change to bone
Describe atherosclerosis
intimal lesions called atheromas/atherosclerotic plaques that protrude into vessel lumens
mechanically obstruct blood flow
plaques can rupture –> vessel thrombosis
plaques weaken underlying media –> aneurysm formation
Describe the appearance of an atheromatous plaque
raised lesion with a soft, yellow core of lipid covered by a white fibrous cap
What are the major targets of atherosclerosis?
large elastic arteries (aorta, carotid and iliac arteries)
medium sized muscular arteries (coronary and popliteal arteries)
Where does symptomatic atherosclerotic disease most commonly affect?
the arteries supplying:
- heart
- brain
- kidneys
- lower extremities
What are the major consequences of atherosclerosis?
myocardial infarction
cerebral infarction
aortic aneurysm
peripheral vascular disease
Atherosclerosis constitutional risk factors
increasing age
male gender
genetic abnormalities
family history
Atherosclerosis modifiable risk factors
hyperlipidemia
hypertension
cigarette smoking
diabetes mellitus
inflammation
Describe the pathogenesis of atherosclerosis
endothelial injury - increased vascular permeability, enhanced leukocyte adhesion, thrombosis
accumulation of lipoproteins
monocyte adhesion to the endothelium - migration into the intima, transformation into macrophages and foam cells
platelet adhesion
factor release - inducing smooth muscle cell recruitment
smooth muscle cell proliferation - ECM production
lipid accumulation - extracellularly and within cells
How does blood flow in straight regions of arteries?
rate of blood flow changes throughout the cardiac cycle but flow is always in the same direction and patterns are laminar
How does blood flow in regions of arteries where they divide or curve sharply?
complex flow patterns develop
flow is slower and can reverse direction during the cardiac cycle (called oscillatory flow)
How does arteries dividing or curving sharply affect atherosclerosis?
endothelial cells in areas of disturbed shear have an activated pro-inflammatory phenotype
poor alignment, high turnover, oxidative stress and expression of inflammatory genes
associated with high susceptibility to atherosclerosis
How do straight regions of arteries affect atherosclerosis?
endothelial cells in these areas have quiescent, anti-inflammatory phenotype
alignment in direction of flow
expression of anti-inflammatory genes
low levels of oxidative stress, cell turnover and permeability
protected from atherosclerosis
Describe fatty streaks
earliest lesions in atherosclerosis
composed of lipid-filled macrophages
not significantly raised and do not cause flow disturbance
seen in almost all children >10
How do fatty streaks relate to atherosclerotic plaques?
relationship uncertain
may evolve into precursors of plaques
Describe the appearance of atherosclerotic plaques
plaques impinge on the lumen of the artery
grossly appear white to yellow
superimposed thrombus over ulcerated plaques is red-brown
0.3-1.5cm in diameter
What are the 3 principal components of atherosclerotic plaques?
cells - smooth muscle cells, macrophages, T cells
ECM - collagen, elastic fibres, proteoglycans
intracellular and extracellular lipid
What are the 4 areas of an atherosclerotic plaque?
superficial fibrous cap
cellular area (beneath and to the side of the cap) - macrophages, T cells, smooth muscle cells
necrotic core (deep to fibrous cap) - lipid, dead cell debris, foam cells, fibrin
neovascularisation - periphery of lesions show proliferating small blood cells
What process can atherosclerotic plaques undergo?
calcification
Clinically important changes atherosclerotic plaques can undergo
rupture, ulceration of erosion of intimal surface - induced thrombosis, can occlude lumen
haemorrhage into a plaque - haematoma can induce plaque rupture
atheroembolism
aneurysm formation - atrophy of underlying media, loss of elastic tissue, causes weakness
How do vulnerable and stable plaques differ?
stable = dense fibrous cap, minimal lipid accumulation, little inflammation
vulnerable (unstable) = thin caps, large lipid cores, relatively dense inflammatory infiltrate
