Atheroma

Question 1

Where are atheromas distributed?

Answer 1

Patchily in elastic arteries and large/medium muscular arteries

Question 2

What are the layers of the arterial wall structure?

Answer 2

Intima - Endothelium (simple squamous), basal lamina, subendothelial connective tissue

Media - thickest, smooth muscle, elastic and collagen fibres

Adventitia - thin outer layer to prevent overstretch - contains vasa vasorum, nervi vascularis

Question 3

What is the structure of a plaque?

Answer 3

1. Fibrous cap - made of smooth muscle, with collagen and elastin
2. Shoulder regions - accumulation of foam cells and T lymphocytes
3. Lipid core - oxidised LDL and cholesterol, cell debris and some foam cells
4. Weak vessel wall under plaque due to degeneration of vessel media

Question 4

What are the stages of plaque development?

Answer 4

1. LDLs damage and enter the endothelium
2. Monocytes attracted
3. Foam cells die
4. Cytokines encourage smooth muscle to form fibrous cap
5. Continued growth and development of nectrotic core
6. Deterioration of plaque

Question 5

How do LDLs damage and enter the endothelium?

Answer 5

Monocytes release free radicals → oxidise LDLs

oxLDL → damages endothelium at points of high shear stress and bind to basement membrane proteoglycans

Question 6

How are monocytes attracted in plaque development?

Answer 6

Damaged endothelium expresses cell surface adhesion molecules for monocytes

Macrophages migrate to subendothelium and take up oxLDL → Foam Cells

Question 7

What happens when foam cells die?

Answer 7

They cannot process LDL, the debris realases further free radicals and attracts more monocytes/T cells

Question 8

How is the fibrous cap formed?

Answer 8

Cytokines cause SMCs to migrate → intima

1. Secrete collagen and elastin → forms cap
2. Encourage angiogenesis into plaque
3. Encourage further SMC migration into plaque/cap

Question 9

How is the necrotic core formed?

Answer 9

Foam cells death → toxic free radicals and cytokines → induction of apoptosis

Question 10

How does the plaque deteriorate?

Answer 10

Macrophage/Foam cells produce factors → SMC death and fibrous cap breakdown

Erosion: Cytokine-induced apoptosis and enzymes cutting basement membrane → endothelium erosion

Question 11

How does thrombosis form?

Answer 11

Erosion/ rupture of the fibrous cap

Question 12

How does rupture occur?

Answer 12

Unstable plaque development:

1. Thin fibrous cap with few SMCs
2. Increased inflammatory cell concentration (especially active macrophages instead of foam)
3. Eroded epithelium

Question 13

How does NO play a role in plaque formation?

Answer 13

Undersecretion

Question 14

When is NO normally secreted? and what are its actions?

Answer 14

In response to shear stress

Vasodilation

Antiatherogenic - inhibits: SMC proliferation, monocyte attraction, LDL oxidation; and antiplatelet effects

Damaged endothelium less likely to be able to produce NO