Atherosclerosis

Question 1

Atherosclerosis?

Answer 1

Chronic inflammatory process affecting the intima of arteries. It sis characterised by the formation of lipid-rich plaques in the vessel wall

Question 2

Modifiable risk factors of atherosclerosis?

Answer 2

The important *modifiable risk factors for developing atherosclerosis are:
• Smoking
• Hypertension
• Diabetes mellitus
• Dyslipidaemia (abnormal lipoprotein levels i.e. high ratio of LDL:HDL)

All four of these risk factors damage the endothelium

Question 3

What happens when the endothelial cells become dysfunctional in atherosclerosis?

Answer 3

• There is increased permeability
• They produce adhesion molecules and cytokines which attract inflammatory cells and prothrombotic molecules. E.g. VCAM-1 (vascular cell adhesion molecule-1) binds monocytes and T cells.

Question 4

What happens as a result of endothelial cell dysfunction?

Answer 4

Consequently, there is recruitment of inflammatory cells to the site of injury: monocytes and T cells adhere to the endothelium and migrate into the intima. The monocytes differentiate into macrophages.

Question 5

What effects do the macrophages have once they are recruited in atherosclerosis?

Answer 5

The macrophages have a number of effects:
• They produce free radicals that drive LDL oxidation to form oxidised LDL
[Remember: native LDL is not atherogenic. Oxidised LDL is highly atherogenic]
• They engulf oxidised LDL and cholesterol crystals, becoming foam cells.
[A foam cell is a macrophage containing abundant lipid in its cytoplasm, giving the cytoplasm a “foamy” appearance microscopically - hence the name].
* Foam cells produce growth factors what stimulate migration of smooth muscle cells from the media to the intima.

Question 6

What is a fatty streak?

Answer 6

Oxidised LDL accumulates within macrophages and smooth muscle cells just underneath the endothelial cells. Collections of lipid-laden macrophages sitting in the intimal layer may be visible as yellow elevations called fatty streaks. The fatty streak has no clinical significance but it is important because it may progress to an atherosclerotic plaque.

Question 7

Atherosclerotic plaque?

Answer 7

A core of lipid debris forms as the foamy macrophages die and the lipid in their cytoplasm is released. Smooth muscle cells proliferate and change their behaviour: they secrete collagen and other extracellular matrix proteins (rather than being contractile), resulting in the formation of a fibrous cap over the core. The core is composed of oxidised lipid and inflammatory cells. The cap represents the body’s attempt to repair scarring.

Question 8

What are the non-modifiable risk factors of atherosclerosis?

Answer 8

Family history and male gender.

Other modifiable risk factors include obesity, diet and exercise.

Question 9

What features of chronic inflammation are seen in atherosclerosis?

Answer 9

1. Persistent injury (endothelial damage due to the previously described risk factors.
2. On-going inflammation (macrophages and lymphocytes)
3. Repair with scarring (the fibrous cap or the plaque)