Atherosclerosis

Question 1

What arteries are affected by atherosclerosis?

Answer 1

Large and medium-sized arteries.

Question 2

What are atheroslcerotic lesions made up from?

Answer 2

Fatty streaks, fibrolipid plaque and complicated (thrombosed) lesions.

Question 3

What are the risk factors for atherosclerosis?

Answer 3

Increasing age
Male gender
Hypertension
Smoking
Diabetes

Question 4

What molecules are associated with atherosclerosis?

Answer 4

Increased LDL
Lp(a)
Fibrinogen
Factor VII
Reduced HDL

Question 5

What is a major consequence of atherosclerosis?

Answer 5

Organ ischaemia

Question 6

Atherosclerosis is characterised by

Answer 6

Formation of focal elevated lesions in the intima of vessels.

Question 7

What causes life threatening damage?

Answer 7

Occlusive thrombosis forms on a spontaneously disrupted plaque (known as atherothrombosis).

Question 8

What is a fatty streak?

Answer 8

Earliest significant lesion - yellow linear elevation of the intimal lining. Composed of masses of lipid-laden macrophages. Can develop to plaques.

Question 9

Describe a fully developed plaque.

Answer 9

A lesion with a central lipid core + fibrous cap covered by arterial endothelium.

Question 10

What is the fibrous cap made up from and what produces this?

Answer 10

Collagen and is made by the smooth muscle cells.

Question 11

What other cell types are found in the fibrous cap?

Answer 11

Macrophages, T-lymphocytes and mast cells.

Question 12

Describe atheromatous lesions.

Answer 12

Rich in cellular lipids and debris.

They are soft, semi-fluid, thrombogenic lesions bordered by foam cells.

Question 13

What are foam cells?

Answer 13

Macrophages that phagocytosed oxidised lipoproteins via special membrane bound scavenger receptors. They have large amounts of cytoplasm with a foamy appearance.

Question 14

Where are plaques most likely to form?

Answer 14

At arterial branching points and bifurcations.

Question 15

What is the most important risk factor?

Answer 15

Hypercholesterolaemia.
Plasma cholesterol levels>8 mmol/L

Question 16

What are the less strong risk factors?

Answer 16

Obesity sedentary lifestyle, low socio-economic status and low birth weight. Recurrent infections with pathogens such as dental pathogens are thought to increase the risk as well. (switching on inflammatory pathways.

Question 17

What are the two steps in the development of atherosclerosis?

Answer 17

1. Injury to the endothelium.
2. Tissue response to the injury.

Question 18

Describe the pathogenesis of plaque formation.

Answer 18

Injury to endothelial cells - increased expression of ICAM-1 (adhesion for monocytes) and E-selectin (high permeability for LDL) and increased thrombogenicity.

Inflammatory cells and lipids enter the intimal layers.

In more advanced stages large amounts of macrophages and T-cells.

Foam cells die via apoptosis - releasing lipids.

Question 19

Describe the steps of tissue repair in lesion formation.

Answer 19

The inflammatory reaction is followed by PDGFs stimulate intimal SMCs -> collagen synthesis, elastin and mucopolysacharride synth.

Fibrous cap encloses the lipid-core.

Question 20

What secretes GFs?

Answer 20

Platelets, injured endothelium, macrophages and SMCs.

Question 21

What is another important mechanism of plaque growth?

Answer 21

Haemorrhage. Rupture or leakage of microvessels within plaque.

Question 22

What are the clinical manifestations?

Answer 22

1. Progressive lumen narrowing due to a high grade plaque stenosis. 50-75% occlusion - reversible.

Stable angina (stenosed coronary artery)
Intermittent claudication (iliac/femoral/popliteal artery).

2. Acute atherothrombotic occlusion= plaque rupture= high thrombogenic components exposed.

Total occlusion leads to necrosis.

3. Embolism= detachment of small thrombus fragment.
   In carotids= cause of stroke
4. Ruptured AAA= retroperitoneal haemorrhage and death.

Question 23

The vulnerable plaque concept

Answer 23

High risk of developing thrombotic complications.

Thin fibrous cap, large lipid core and inflammation due to proteolytic enzymes, CKs, ROS.

Question 24

Preventative and therapeutic approaches.

Answer 24

• Smoking cessation
• BP control
• Weight reduction
• Regular exercise
• Dietary modifications
• Statins (inhibit HMG CoA reductase enzyme (rate limiting in hepatic cholesterol synthesis).
• Low dose of aspirin inhibits platelet aggregation.

Surgical:
- Endarterectomy intima is cored out from the underlying media.
- Percutaneous angioplasty crack open atheromatous plaques by using an inflatable balloon.
- Bypass - saphenous vein or fabric grafts