Atherosclerosis

Question 1

What are the 3 main stages in the development of atherosclerosis?

Answer 1

1. endothelial damage
2. uptake of modified LDL particles, adhesion and infiltration of macrophages
3. SMC proliferation and formation of fibrous cap

Question 2

Explain the role of LDLs in atherosclerosis.

Answer 2

LDLs become trapped int he subendothelial space and can be oxidised or glycated
This modification means that the LDLs are not recognised by receptors and their accumulation does not trigger negative feedback
LDLs are taken up by scavenger receptors
The accumulation of LDL allows for foam cells to form

Question 3

Explain the role of macrophages in atherosclerosis.

Answer 3

Monocytes cross endothelium where they are transformed/differentiate into macrophages
Macrophages proliferate locally
They ingest the oxidised LDLs
This forms foam cells
Can lead to the formation of fatty streaks

Question 4

How is the fibrous cap formed in atherosclerosis?

Answer 4

The foam cells and platelets encourage the migration and proliferation of smooth muscle cells (release PDGF)
SMCs proliferate into the intima and collagen production begins
SMCs become foam cells due to uptake of modified LDL
Collagen forms a fibrous cap (this is fragile)

Question 5

What are the risk factors for atherosclerosis?

Answer 5

Increasing age
Male
Hyperlipidaemia/dyslipidaemia
Smoking
HTN
Chlamydia (emerging RF)
Lipoprotein A (emerging RF)
Homocysteinaemia (emerging RF)
Family history
Physical inactivity
Diabetes mellitus

Question 6

What are the ideal levels of:

• total cholesterol
• LDL
• HDL
• triglycerides

Answer 6

Total cholesterol: <200 mg/dL
LDL: <130 mg/dL
HDL: >40 mg/dL
Triglycerides: <150 mg/dL

Question 7

How can atherosclerosis be prevented?

Answer 7

Reduce blood cholesterol: diet, exercise, smoking/alcohol/drugs
Plasma lipid reduction using cholesterol

Question 8

What are the potential complications of atherosclerosis?

Answer 8

1. Coronary artery disease - angina, MI
2. Peripheral vascular disease - arterial occlusive disease, ulcers, peripheral neuropathy, gangrene
3. Stroke
4. Aneurysm
5. Renal artery stenosis