CVS 18: Atherosclerosis

Question 1

Give some modifiable and non-modifiable risk factors for atherosclerosis

Answer 1

Modifiable:
  - smoking
  - lipids
  - BP
  - Diabetes
  - obesity
  - Lack of exercise
Non-modifiable:
  - age
  - sex
  - genetic background
Presence of two or more risk factors multiplies the associated risks

Question 2

Where does atherosclerosis tend to occur?

Answer 2

• when it goes around a corner too quickly –> sets up EDDYs (turbulent flow)
• tend to be in outside of bend
• bifurcations (of the common carotid)

Question 3

Where do LDLs deposit in atherosclerosis? What does it bind to?

Answer 3

• Deposit in the suboptimal space

- binds to matrix proteoglycans

Question 4

What happens once LDLs have been deposited?

Answer 4

• LDLs deposit and are stuck because of proteoglycans
• LDLs oxidised because it is a very oxidative environment
• Macrophages phagocytose LDLs
• Foam cell formation
• fat deposition around macrophages because they can’t phagocytose any more
• fat builds up and you get core of EC lipid –> join to form one large mass of fat
• inflammation irritates interior of plaque => fibrous thickening
• macrophages release growth factors –> stimulate SMCs to grow, divide and make more collagen
• plaque ruptures - lipid core which is thrombogenic communicates with lumen –> clot formation in lumen

Question 5

What are the five main cell types, explain their function

Answer 5

1. Vascular endothelial cells: barrier function, leukocyte recruitment
2. Platelets- thrombus generation, cytokine and GF release
3. Monocyte- macrophages: foam cell formation, cytokine release, free radical source, metalloproteinases
4. VSMCs- migration and proliferation, collagen synthesis, remodelling and fibrous cap formation
5. T lymphocytes: macrophage activation

Question 6

What are the normal and abnormal functions of free-radicals used by macrophages?

Answer 6

• normally used to kill microbes

- abnormal inflammatory action=> become source of free radicals

Question 7

What are matrix metalloproteinases?

Answer 7

degrade the ECM proteins such as collagens

Question 8

What are the main inflammatory cells in atherosclerosis?

Answer 8

Macrophages

Question 9

What are the two main classes of macrophages?

Answer 9

1. resident = mainly homeostatic

2. inflammatory = kill microorganisms

Question 10

What are the different roles of resident macrophages

Answer 10

• suppress inflammatory activity
• alveolar resident macrophages (surfactant liid homeostasis)
• Osteoclasts (calcium and phosphate homeostasis)
• spleen (iron homeostasis)