Atherosclerosis Part 2 (Nichols)

Question 1

What role do oxidative stress and hypochlorous acid (product of myeloperoxidase) play in CVD?

Answer 1

They both promote apoptosis of endothelial cells that causes erosion of the atheroma that can lead to atheroma rupture, exposure of the lipid core containing prothrombotics, and development of a thrombus that can occlude the vessel at that site, or downstream.

Question 2

What procoagulant factor do endothelial cells produce when undergoing apoptosis?

Answer 2

Tissue Factor

Question 3

What degrade collagen fibrous caps, making the atheroma more “vulnerable” to rupture?

Answer 3

MMPs (1, 2, 8, 13*, 14)

* denotes relative importance in degradation of collagen

Question 4

What is Lp-PLA2 and what role does it play in CVD?

Answer 4

Circulates with LDL. Is proinflammatory. Its products upregulate expression of monocyte chemoattractant protein-1 (MCP-1), ICAM-1, and VCAM-1 on endothelial cells, making them respond less to NO and to undergo apoptosis. Is an independent predictor of CVD.

Question 5

What plays a larger role in ischemia, infarction, and death:
lumenal stenosis by an unruptured atheroma, or rupture of a vulnerable plaque and subsequent thrombus formation and rapid occlusion of the vessel lumen?

Answer 5

Vulnerable plaques

Question 6

What are the 4 determinants of vulnerability of a plaque?

Answer 6

1) thinness of the fibrous cap
2) size of the lipid (necrotic) core
3) amount of inflammation
4) amount of calcification

Question 7

What have been found to be a more important first line therapy in preventing CVD events:
Aspirin or statins?

Answer 7

Statins come first.

Question 8

How do statins prevent acute coronary atherosclerotic events?

Answer 8

Lipid lowering can increase the fibrous nature of plaques, reducing their vulnerability, which is the most important determinant of disease progression.

Question 9

What product of activated T-cells strongly inhibits the ability of SM cells to make the new collagen required to repair and maintain the integrity of the fibrous cap of atheromas?

Answer 9

IFN-gamma

Question 10

Macrophages overproduce these factors that are especially good at degrading collagen of fibrous caps of atheromas:

Answer 10

MMP-1, 8, 13 “interstitial collagenases”

Question 11

How do T-cells and macrophages work together to produce factors that degrade collagen of fibrous caps of atheromas?

Answer 11

Via CD40 on macrophages. T-cells produce CD40 ligand that boosts the production of interstitial collagenases by macrophages.

Question 12

List, in descending order, the arteries most extensively involved in atherosclerosis.

Answer 12

Lower abdominal aorta, coronary arteries, popliteal arteries, internal carotid arteries, and the vessels of the circle of Willis.

Question 13

Describe the distribution of acute coronary disease in the LAD, RCA, and left circumflex artery (LCX).

Answer 13

1/2 LAD*
1/3 RCA
1/6 LCX

Question 14

At early stages of stenosis, what can occur that tends to preserve the size of the lumen?

Answer 14

Remodeling of the artery, expanding it outward (dilating it, sort of) tends to preserve the size of the lumen. This is def. not a permanent solution.

Question 15

What is critical stenosis?

Answer 15

the stage at which the occlusion is sufficiently severe to produce tissue ischemia. (70% occlusion)
Pain upon exertion will been seen at this stage in the form of angina if the coronary arteries are affected.

Question 16

Acute plaque changes fall into three general categories (have three fates):

Answer 16

1) rupture, releasing highly thrombogenic plaque constituents into the bloodstream –> embolus
2) erosion, exposing the thrombogenic subendothelial basement membrane to blood –> thrombus formation
3) hemorrhage into the atheroma, expanding volume