Atherogenesis

Question 1

Define arteriosclerosis

Answer 1

hardening of the arteries
generic term reflecting arterial wall thickening and loss of elasticity

Question 2

Name the 3 general patterns of arteriosclerosis

Answer 2

arteriolosclerosis
Monckeberg medial sclerosis
atherosclerosis

Question 3

Describe arteriolosclerosis

Answer 3

small arteries and arterioles
downstream ischaemic injury
anatomic variants, hyaline and hyperplastic
associated with diabetes and hypertension

Question 4

Describe Monckeberg medial sclerosis

Answer 4

generally patients >50
calcific deposits (does not occlude artery lumen)
may undergo metaplastic change to bone

Question 5

Describe atherosclerosis

Answer 5

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

Question 6

Describe the appearance of an atheromatous plaque

Answer 6

raised lesion with a soft, yellow core of lipid covered by a white fibrous cap

Question 7

What are the major targets of atherosclerosis?

Answer 7

large elastic arteries (aorta, carotid and iliac arteries)

medium sized muscular arteries (coronary and popliteal arteries)

Question 8

Where does symptomatic atherosclerotic disease most commonly affect?

Answer 8

the arteries supplying:
- heart
- brain
- kidneys
- lower extremities

Question 9

What are the major consequences of atherosclerosis?

Answer 9

myocardial infarction
cerebral infarction
aortic aneurysm
peripheral vascular disease

Question 10

Atherosclerosis constitutional risk factors

Answer 10

increasing age
male gender
genetic abnormalities
family history

Question 11

Atherosclerosis modifiable risk factors

Answer 11

hyperlipidemia
hypertension
cigarette smoking
diabetes mellitus
inflammation

Question 12

Describe the pathogenesis of atherosclerosis

Answer 12

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

Question 13

How does blood flow in straight regions of arteries?

Answer 13

rate of blood flow changes throughout the cardiac cycle but flow is always in the same direction and patterns are laminar

Question 14

How does blood flow in regions of arteries where they divide or curve sharply?

Answer 14

complex flow patterns develop
flow is slower and can reverse direction during the cardiac cycle (called oscillatory flow)

Question 15

How does arteries dividing or curving sharply affect atherosclerosis?

Answer 15

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

Question 16

How do straight regions of arteries affect atherosclerosis?

Answer 16

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

Question 17

Describe fatty streaks

Answer 17

earliest lesions in atherosclerosis
composed of lipid-filled macrophages
not significantly raised and do not cause flow disturbance
seen in almost all children >10

Question 18

How do fatty streaks relate to atherosclerotic plaques?

Answer 18

relationship uncertain
may evolve into precursors of plaques

Question 19

Describe the appearance of atherosclerotic plaques

Answer 19

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

Question 20

What are the 3 principal components of atherosclerotic plaques?

Answer 20

cells - smooth muscle cells, macrophages, T cells

ECM - collagen, elastic fibres, proteoglycans

intracellular and extracellular lipid

Question 21

What are the 4 areas of an atherosclerotic plaque?

Answer 21

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

Question 22

What process can atherosclerotic plaques undergo?

Answer 22

calcification

Question 23

Clinically important changes atherosclerotic plaques can undergo

Answer 23

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

Question 24

How do vulnerable and stable plaques differ?

Answer 24

stable = dense fibrous cap, minimal lipid accumulation, little inflammation

vulnerable (unstable) = thin caps, large lipid cores, relatively dense inflammatory infiltrate

Question 25

Summary of how MI affects heart tissue

Answer 25

myocardial infarction
acute inflammation
tissue digestion/phagocytosis
inflammation, resolution, neovascularisation, scar formation, wound healing