Atherosclerosis

Question 1

Atherosclerosis is a chronic ______ response in the walls of arteries associated with collection of ______ that accumulate _____ (primarily cholesterol, from LDL) and _____ ______ deposits from fibroblasts.

Answer 1

A chronic inflammatory response in the walls of arteries associated with collection of macrophages that accumulate lipids (primarily cholesterol, from LDL) and collagen matrix deposits from fibroblasts.

Question 2

steps in development of atherosclerosis

Answer 2

1. Endothelial cell injury
2. Macrophage and lymphocyte migration
3. Lipid accumulation, smooth muscle-fibroblast proliferation
4. Plaque structure evolution

Question 3

Injury of vascular endothelium results in ______ cell activation and produces a pro-_______, pro-_____ state

Answer 3

Injury of vascular endothelium results in endothelial cell activation and produces a pro-thrombotic, pro-atherogenic state

Question 4

endothelial cell injuries

Answer 4

• HTN (mechanical stress)
• Flow disturbance (slow, turbulent flow)
• Smoking, pollution (?)
• Hyperglycemia
• High LDL concentration (oxidized LDL, small dense LDL)
• Immune injury

Question 5

_______ cells express selective _______ molecules that bind ______ and inflammatory mediators

Answer 5

Endothelial cells express selective adhesion molecules that bind monocytes and inflammatory mediators

Question 6

what 2 things migrate between endothelial cells and localize in the intima (space between EC and basement membrane)

Answer 6

macrophages and lymphocytes

Question 7

what engulf LDL, especially oxidized LDL

Answer 7

macrophages

Question 8

What is LDL oxidized by?

Answer 8

• oxygen free radicals (inflammation)

- slow and turbulent blood flow

Question 9

What is LDL enhanced by?

Answer 9

-small size of LDL –> “small dense LDL”

Question 10

What become activated and promote chronic inflammation?

Answer 10

T lymphocytes

Question 11

What do activated macrophages do to LDL

Answer 11

phagocytose LDL

Question 12

What does phagocytosis of LDL cause?

Answer 12

release of O2 radicals

Question 13

What does the release of O2 radicals do to LDL?

Answer 13

oxidize addition LDL, further increasing LDL uptake

Question 14

What does the activation of macrophages and LDL uptake result in?

Answer 14

• lipid inclusions in macrophages

- secrete growth factors

Question 15

What are lipid rich macrophages?

Answer 15

foam cells

Question 16

_______ macrophages release ______, forming ____ _____ of atherosclerotic lesion.

Answer 16

Dying macrophages release lipids, forming lipid core of atherosclerotic lesion.

Question 17

What do growth factors promote?

Answer 17

promote migration and proliferation of smooth muscle and fibroblasts into lesions

Question 18

Dense collagen-rich matrix from smooth muscle and fibroblasts

Answer 18

superficial fibrous cap

Question 19

actively expanding edge of the lesion

Answer 19

“shoulder” of cap

Question 20

What makes up the central core? (3)

Answer 20

• Lipid-containing foam cells
• Fatty debris (lipid core, cholesterol crystals)
• Necrotic cellular debris

Question 21

Unstable plaques contain:

Answer 21

• Large lipid core or intraplaque hemorrhage
• Thin or easily ruptured cap
• Marked inflammatory component

Question 22

Stable plaques contain:

Answer 22

• Mainly fibrous with thick continuous fibrous cap
• Small or no lipid core
• Little sign of inflammation

Question 23

large lipid core or intraplaque hemorrhage

Answer 23

unstable plaque

Question 24

small or no lipid core

Answer 24

stable plaque

Question 25

thin or easily ruptured cap

Answer 25

unstable plaque

Question 26

mainly fibrous with thick continuous fibrous cap

Answer 26

stable plaque

Question 27

marked inflammatory component

Answer 27

unstable plaque

Question 28

little sign of inflammation

Answer 28

stable plaque

Question 29

What type of plaque is more likely to rupture, resulting in thrombosis ± embolus formation? i.e. MI

Answer 29

unstable plaque

Question 30

What type of plaque is more likely to result in gradual stenosis and tissue ischemia? i.e. angina, claudication

Answer 30

stable plaque

Question 31

What does increase in plaque size cause? (3)

Answer 31

• arterial dilation
• arterial wall thickening and plaque enlargement
• stenosis

Question 32

Regarding plaque size increase, what does arterial dilation result in?

Answer 32

minimal internal diameter change (positive remodeling, an early response)

Question 33

Regarding plaque size increase, what does arterial wall thickening and plaque enlargement result in?

Answer 33

internal diameter reduction (negative remodeling)

Question 34

Regarding plaque size increase, what does stenosis result in?

Answer 34

reduction in internal diameter for any reason, including plaque accumulation

Question 35

gradual thickening of the arterial wall at an area of injury (enhanced healing response)

Answer 35

restenosis

Question 36

What can insertion of vascular stent or angioplasty cause?

Answer 36

vascular injury, often causing restenosis

Question 37

What can inhibit restenosis to maintain lumen size longer?

Answer 37

drug-eluding stents

Question 38

What results in endothelial cell activation and plaque formation?

Answer 38

disruptions in laminar (straight, undisturbed) blood flow

Question 39

examples of where plaques form when and where flow is disrupted

Answer 39

• Vessel bifurcations (internal/external carotid)
• Vessel branches (circle of Willis, intercostal arteries)
• Areas of blood stasis (Carotid bulb)

Question 40

Plaques expand in _____, _____, and ____ i.e. remodel

Answer 40

Plaques expand in length, width, and depth i.e. remodel