Atherosclerosis and Restenosis

Question 0

Review: Are thin fibrous caps or thick fibrous caps on plaques more likely to rupture?

Answer 0

Thin are more likely to rupture.

Question 1

What did the COURAGE trial comparing percutaneous catheter intervention (PCI) to medical Rx for STABLE angina show? (2007)

Answer 1

No benefit from PCI over medical Rx.

Remember this is stable angina.

Question 2

What’s a Type I atherosclerotic lesion?

Answer 2

Isolated macrophage / foam cells

Question 3

What’s a Type II atherosclerotic lesion?

Answer 3

Fatty streak - still mostly intracellular lipids

Question 4

What’s a Type III atherosclerotic lesion?

Answer 4

Extracellular lipid pools appear.

Question 5

What’s a Type IV atherosclerotic lesion?

Answer 5

An atheroma - a lipid core develops in the neointima.

Question 6

What’s a Type V atherosclerotic lesion?

Answer 6

A fibroatheroma - there’s a lipid core and fibrotic changes… can be multiple cores. Calcification can be present.

Question 7

What’s a Type VI atherosclerotic lesion?

Answer 7

Complicated - surface defects, thrombus, hemorrhage

Question 8

What’s one cytokine-receptor pair involved in recruiting monocytes to fatty streaks (Type I)?

Answer 8

CCR2 on monocytes sees MCP-1

Question 9

Stable angina is most likely caused by what kind of lesions?

Answer 9

Fibrotic plaques with a thick cap, lots of SMC activity, partially occluding coronary arteries.

Question 10

What limits the long-term effectiveness of stenting partially occluded arteries? What cell type mediates this process?

Answer 10

Restenosis.

SMCs mediate this process as a response to endothelial damage caused by the stend.

Question 11

Does restenosis resemble atherosclerosis?

Answer 11

Nope. Restenosis is driven by SMCs and matrix deposition, not lipid accumulation.

Question 12

4 vascular growth factors that mediate restenosis?

Answer 12

PDGF
basic FGF
A-II
TGFbeta

Question 13

What does PDGF (platelet-derived growth factor) do in restenosis?

Answer 13

PDGF (which here comes from endothelial cells and macrophages, not just platelets) is a chemoattractant for SMCs to migrate to the intima from the media.

Question 14

What does basic FGF do in restenosis? What makes it, when is it made?

Answer 14

basic FGF is made by SMCs in response to stretch/damage (perhaps during balloon inflation), and causes proliferation of SMCs.

Question 15

How might A-II be involved in restenosis?

Answer 15

Promotes proliferation of SMCs.

in rats… ACE inhibition has been shown to decreased restenosis in rats, but not in humans

Question 16

In restenosis, what makes TGFbeta, and what does it do?

Answer 16

SMCs, endothelial cells, and platelets make TGFbeta.

TGFbeta stimulates SMCs to lay down ECM.

Question 17

How do rapamycin and paclitaxel-eluting stents help reduce restenosis?

Answer 17

By inhibiting SMC proliferation.

Question 18

Major risk with drug-eluting stents?

Answer 18

Late thrombosis - (perhaps because atherosclerotic plaques can’t form a strong fibrous cap w/o SMC activity)

Question 19

Why is restenosis considered “predictable”?

Answer 19

If it doesn’t happen in the first 6mo post PCI, it’s probably not going to happen.