Where are atheromas distributed?
Patchily in elastic arteries and large/medium muscular arteries
What are the layers of the arterial wall structure?
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
What is the structure of a plaque?
- Fibrous cap - made of smooth muscle, with collagen and elastin
- Shoulder regions - accumulation of foam cells and T lymphocytes
- Lipid core - oxidised LDL and cholesterol, cell debris and some foam cells
- Weak vessel wall under plaque due to degeneration of vessel media
What are the stages of plaque development?
- LDLs damage and enter the endothelium
- Monocytes attracted
- Foam cells die
- Cytokines encourage smooth muscle to form fibrous cap
- Continued growth and development of nectrotic core
- Deterioration of plaque
How do LDLs damage and enter the endothelium?
Monocytes release free radicals → oxidise LDLs
oxLDL → damages endothelium at points of high shear stress and bind to basement membrane proteoglycans
How are monocytes attracted in plaque development?
Damaged endothelium expresses cell surface adhesion molecules for monocytes
Macrophages migrate to subendothelium and take up oxLDL → Foam Cells
What happens when foam cells die?
They cannot process LDL, the debris realases further free radicals and attracts more monocytes/T cells
How is the fibrous cap formed?
Cytokines cause SMCs to migrate → intima
- Secrete collagen and elastin → forms cap
- Encourage angiogenesis into plaque
- Encourage further SMC migration into plaque/cap
How is the necrotic core formed?
Foam cells death → toxic free radicals and cytokines → induction of apoptosis
How does the plaque deteriorate?
Macrophage/Foam cells produce factors → SMC death and fibrous cap breakdown
Erosion: Cytokine-induced apoptosis and enzymes cutting basement membrane → endothelium erosion
How does thrombosis form?
Erosion/ rupture of the fibrous cap
How does rupture occur?
Unstable plaque development:
- Thin fibrous cap with few SMCs
- Increased inflammatory cell concentration (especially active macrophages instead of foam)
- Eroded epithelium
How does NO play a role in plaque formation?
Undersecretion
When is NO normally secreted? and what are its actions?
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
