Inflammation and Atherogenesis

Question 1

What is the pathophysiology of inflammation in atherogenesis?

Answer 1

You should know this from previous lectures:

LDL gets into subendotheilal space–> LDL is oxidized and becomes pro-inflammatory–>Cytokines attract monocytes which diapedis–> monocytes eat LDL and become Foam Cells.

*Note: other cells such as T-cells, Mast cells and platelets also play a role in inflammation

Question 2

What is the role of monocytes in atherogenesis? Name an important cell adhesion receptor that is involved in margination of monocytes.

Answer 2

Monocytes eat LDL and become Foam Cells.

VCAM-1 is a potential target for therapy due to its involvement in margination,

Question 3

Which T-cell is thought to have a pro-inflammatory effect in atherogenesis?
Th1
Th2
Treg

Answer 3

Th1 is pro-inflammatory
Th2- not really associated
Treg- anti-inflammatory effect

Question 4

The innate immune system is thought to initiate injury in atherogenesis. What cell helps facilitate the transition from innate to acquired?

Answer 4

Dendritic cells.

Question 5

What are the major drivers of formation of an unstable plaque and eventual MI?

Answer 5

1. Macrophage apoptosis/necroses creates a “necrotic core”
2. Weakening of fibrotic cap via MMPs and intra-plaque hemorrhage.
3. Rupture

Question 6

According to clinical trails, rank the following in order of highest to lowest risk for MI

High LDL, low CRP
Low LDL, Low CRP
Low LDL, High CRP
High LDL, High CRP

Answer 6

Most:

High LDL, High CRP
Low LDL, High CRP
High LDL, Low CRP
Low LDL, Low CRP

Yes this is correct.

Take home, CRP levels predict risk of CV events.

Question 7

What happens to patients with normal cholesteral and high CRP when treated with a statin?

Answer 7

Their risk for MIs decreases from 6% to 2% over a few years. This is due to statins ability have more than just reduced cholesterol effects,

Question 8

True or false:

Patients with autoimmune disorders have decreased risk of atherogenesis because their body doesn’t amount a good immune response.

Answer 8

FALSE:

Patients with AI have INCREASED risk.

Question 9

What has greater effect on reducing CV events: High HDL or high HDL cholesterol efflux capacity?

Answer 9

High HDL cholesterol efflux capacity.

• according to most recent research studies. However this is more of a research tool than a diagnostic tool.
• *this also explains why drugs that increase HDL have not reduced CV event risk.

Question 10

Patients with Psoriasis have greater risks for developing CV events. Suggest a possible reason for this observation.

Answer 10

Psoriasis causes impaired HDL efflux capacity.

Question 11

TNF alpha has what effect on CV events?

Answer 11

Increased. TNF alpha inhibitors are a potential drug therapy.

Question 12

Predinsone has what effect on CV events?

Answer 12

Increased