Atherogenesis

Question 1

Risk factors for atherogenesis

Answer 1

Age
Tobacco - endothelial damage
Obesity - adipocytes secrete inflammatory cytokines
Diabetes - hyperglycaemia
Hypertension

Question 2

What are inflammatory cytokines?

Answer 2

Proteins that promote systemic/chronic inflammation

Question 3

Distribution of atherosclerotic plaques

Answer 3

within peripheral and coronary arteries
focal D along artery length
Common in bifrucations

Question 4

Structure of atherosclerotic plaque

Answer 4

Lipid, necrotic core, connective tissue, fibrous “cap”

Question 5

Response to injury hypothesis of atherosclerosis

Answer 5

This is the principle of how these lesions develop
- Initiated by an injury to the endothelial cells which leads to endothelial dysfunction
- Signals sent to circulating leukocytes which then accumulate and migrate into the vessel wall.
- Inflammation ensues
Injury could be: smoking, viral damage, increased cholesterol

Question 6

Examples of when inflammation can be good

Answer 6

pathogens, parasites, tumors, wound healing

Question 7

Igniting inflammation in the arterial wall

Answer 7

LDL – can pass in and out of arterial wall in excess, accumulates in arterial wall, undergoes oxidation and glycation
Endothelial dysfunction (response to injury hypothesis)

Question 8

Stimulus: adhesion

Answer 8

Once initiated, chemoattractants (chemicals that attract leukocytes) are released from endothelium and send signals to leukocytes

Chemoattractants released from site of injury and a concentration-gradient is produced.
It is mainly monocytes that are found in plaques. (1 of the 5 types of WBCs)

Question 9

Inflammatory cytokines found in plaques

Answer 9

IL-1
IL-6
IL-8
IFN-Y
TGF-B
MCP-1
(C reactive protein)

Question 10

Leukocyte recruitment to vessel walls

Answer 10

governed by molecules in the wall.

Defects could lead to a speeding up of these processes

Question 11

Progression of atherosclerosis. What are the 5 stages?

Answer 11

1. Fatty streaks
2. Intermediate lesions
3. Fibrous plaques or advanced lesions
4. Plaque rupture
5. Plaque erosion

Question 12

What happens at fatty streak stage of atherosclerosis (stage 1)?

Answer 12

Earliest lesion of atherosclerosis

Appear at a very early age (

Question 13

What are the components in the intermediate lesions stage of atherosclerosis? (stage 2)

Answer 13

lipid laden macrophages (foam cells)
Vascular smooth muscle cells
T lymphocytes
Adhesion and aggregation of platelets to vessel wall
Isolate pools of extracellular lipid

Question 14

Fibrous plaques/advanced lesions stage characteristics (stage 3)

Answer 14

• Impedes blood flow
• Prone to rupture
• Convered by dense fibrous cap made of ECM proteins including collagen (strength) and elastin (flexibility) laid down by SMC that overlies lipid core and necrotic debris
• May be calcified
• Contains: smooth muscle cells, macrophages and foam cells and T lymphocytes

Question 15

What happens at plaque rupture stage? (stage 4)

Answer 15

• Plaques constantly growing and receding
• Fibrous cap has to be resorbed and redeposited in order to be maintained
• If balance shifted e.g. in favour of inflammatory conditions (increased enzyme activity), the cap becomes weak and the plaque ruptures
• Basement membrane, collagen, and necrotic tissue exposure as well as haemorrhage of vessels within the plaque
• Thrombus (clot) formation and vessel occlusion

Question 16

Plaque erosion stage, what happens (stage 5)

Answer 16

• Second most prevalent cause of coronary thrombosis
• Lesions tend to be small ‘early lesions’
• Fibrous cap does not disrupt
• Luminal surface underneath the clot may not have endothelium present but is smooth muscle cell rich
• There may be a prominent lipid core