CVS atheroma and infarction

Question 1

What are the key components of atheromatous plaques?

Answer 1

1. Fibrous cap
2. Cellular layer
3. Necrotic core

Question 2

Where are the most common sites of plaque build up?

Answer 2

1. Circle of Willis
2. Carotid arteries
3. Coronary arteries
4. Aorta
5. Iliac arteries

Question 3

What are the steps involved in the initiation of plaque formation?

Answer 3

❶ Circulating inflammatory mediators activate endothelial cells which become dysregulated
and express cytokines and adhesion molecules (e.g. vascular cell adhesion molecule (VCAM-1)
❷. Circulating monocytes bind to the activated endothelium (rolling hypothesis) and migrate
between endothelial cells in the intimal tissue ❸. Monocytes differentiate into tissue
macrophages and release inflammatory cytokines into the intima ❹

Question 4

What are the steps involved in plaque formation?

Answer 4

❶ Macrophages upregulate scavenging receptors which allows the uptake of LDL and
conversion of macrophages into lipid-laden foam cells. ❷ Further release of proinflammatory
mediators stimulates vascular smooth muscle cells to migrate from the media into the intimal
space ❸. Vascular smooth muscle cells release growth factors that stimulate cell division and
proliferation as well as synthesizing collagen and elastin. This is known as the ‘synthetic
phenotype’ as VSMCs loose their contractile properties ❹

Question 5

What are the steps involved in the maturation of plaque?

Answer 5

❶ Smooth muscle cells also start to accumulate LDL becoming smooth muscle foam cells. ❷
Both types of foam cell eventually undergo apoptotic cell death releasing pools of lipid that
accumulate forming an expanding lipid core within the intimal layer called an atheroma. ❸ A
fibrous plaque of extracellular matrix components elastin and collagen forms a layer above the atheroma resulting in a fibroatheroma ❹

Question 6

What step is involved in the calcification of plaque?

Answer 6

❶ Calcium is deposited by foam cells that hardens the atheroma and can be used clinically as a marker of atherosclerosis by imaging techniques.

Question 7

What is the step in plaque rupture?

Answer 7

❶ The lipid core can become necrotic and start to fracture and fragment creating fissures
within the core. It can rupture through the endothelial layer causing trauma and exposing
subendothelial collagen and tissue factor to the blood. This initiates the clotting cascade
forming a thrombus.

Question 8

What are the consequences of atheroma?

Answer 8

1. Occlusive thrombosis e.g. myocardial infarction
2. Thromboembolism e.g. Ischaemic stroke
3. Peripheral vascular disease
4. Aneurysm due to wall weakness

Question 9

What is stable cardiac angina due to?

Answer 9

Due to permanent flow limitation

Question 10

What is unstable cardiac angina due to?

Answer 10

Due to transient thrombosis

Question 11

What is myocardial infarction due to?

Answer 11

Due to complete occlusion

Question 12

What are ECG changes and cardiac biomarkers that indicate myocardial infarction?

Answer 12

-ST Elevated Myocardial Infarction: STEMI
-Elevated cardiac troponins e.g. cTnT = necrosis

Question 13

What are surgical interventions to treat myocardial infarction?

Answer 13

Surgical intervention
* Balloon angioplasty
* Stent
* Coronary bypass

Question 14

What are pharmacological treatments for MI and ischaemic stroke?

Answer 14

tPA and a bacterial plasminogen activator,
streptokinase, are used in therapeutic thrombolysis for myocardial infarction and stroke (clot busters)

Question 15

What does tissue plasminogen activator do?

Answer 15

1. Converts plasminogen into plasmin
2. This leads to D dimers being generated when cross-linked fibrin is degraded.

Question 16

When are FDP(fibrin degradation products) generated?

Answer 16

FDP (fibrin degradation products) are generated if non-cross linked fibrin
or fibrinogen is broken down.