PVD and Atherosclerosis

Question 1

What are modifiable risk factors in atherosclerosis development

Answer 1

Smoking
Lipid intake
BP
Diabetes
Obesity
Sedentary lifestyle

Question 2

What are non modifiable risk factors in atherosclerosis development

Answer 2

Age
Sex
Genetic background

Question 3

How much do risk factors increase risk of developing atherosclerosis?

Answer 3

A lot, the risk also severely increases when multiple risk factors are involved

Question 4

What layer does atherosclerosis start in?

Answer 4

Tunica intima

Question 5

What are the stages of atherosclerosis progression called?

Answer 5

Coronary artery at lesion prone location
Type 2 lesion
Preatheroma
Atheroma
Fibroatheroma
Complicated lesion

Question 6

At what stage of atherosclerosis progression do foam cells form?

Answer 6

Type II lesion

Question 7

What is the role of vascular endothelial cells in atherosclerosis

Answer 7

Barrier function (eg to lipoproteins
Leukocyte recruitment

Question 8

What is the role of monocyte/macrophages in atherosclerosis?

Answer 8

Foam cell formation
Cytokine and growth factor release
Major source of free radicals
Metalloproteinases

Question 9

What is the role of platelets in atherosclerosis?

Answer 9

Thrombus generation

Cytokine and growth factor release

Question 10

What is the role of platelets in vascular smooth muscle cells?

Answer 10

Migration and proliferation
Collagen synthesis
Remodelling and fibrous cap formation

Question 11

What is the role of T lymphocytes in atherosclerosis?

Answer 11

Macrophage activation

Question 12

What are the main inflammatory cells in atherosclerosis?

Answer 12

Macrophages

Question 13

What are macrophages derived from in atherosclerosis?

Answer 13

Monocytes

Question 14

What are the 2 main types of macrophages?

Answer 14

Inflammatory

Resident

Question 15

What do inflammatory macrophages do?

Answer 15

They are adapted to kill microorgansims

Question 16

What so resident macrophages do?

Answer 16

They are normally homeostatic and suppress inflammatory activity

Question 17

What is the role of macrophages in the alveoli?

Answer 17

They are for surfactant lipid homeostasis

Question 18

What is the role of macrophages in the osteoclasts?

Answer 18

For calcium and phosphate homeostasis

Question 19

What is the role of macrophages in the spleen?

Answer 19

Iron homeostasis

Question 20

Where is LDL synthesised?

Answer 20

In the liver

Question 21

What is the role of LDL

Answer 21

Transport of cholesterol from the liver to the rest of the body (its bad cholesterol)

Question 22

What is the role of HDL

Answer 22

Reverse cholesterol transport (from the body back to the liver)

Question 23

What type of LDL is highly inflammatory and toxic

Answer 23

Oxidised or modified LDL

Question 24

How is LDL trapped in the subendothelial space?

Answer 24

It binds to sticky carbohydrates in the matrix eg proteoglycans

Question 25

What happens to LDL in the subendothelial space?

Answer 25

After becoming oxidised it is phagocytosed by macrophages and stimulates chronic inflammation

Question 26

How is familial hypercholesterolaemia inherited?

Answer 26

Autosomal

Question 27

What happens in familial hypercholesterolaemia and why?

Answer 27

Cholesterol becomes massively elevated due to deficiency of the LDL receptor in the liver

Question 28

What does a deficiency of LDL receptors in the liver cause (eg in FH)?

Answer 28

Causes macrophages to accumulate cholesterol

Question 29

What cholesterol level illicits recommendation for statins?

Answer 29

Above 5 mmol/L

Question 30

What is cholesterol level in FH?

Answer 30

Above 20 mmol/L

Question 31

How does FH present?

Answer 31

Xanthomas and early atherosclerosis

Question 32

What is the second LDL receptor in atherosclerotic lesions called?

Answer 32

Scavenger receptors

Question 33

What do scavenger receptors do?

Answer 33

They mop up chemically modified LDL

Question 34

What do statins inhibit?

Answer 34

HMG coA reductase

Question 35

What are the 2 types of scavenger receptors?

Answer 35

A and B

Question 36

What do type A scavenger receptors bind to?

Answer 36

Oxidised LDL Gram positive bacteria Dead cells

Question 37

What do type B scavenger receptors bind to?

Answer 37

Oxidised LDL Malaria parasites Dead cells

Question 38

How do macrophages oxidise LDLs?

Answer 38

They have oxidative enzymes

Question 39

What oxidative enzymes do macrophages contain?

Answer 39

NADPH oxidase | Myeloperoxidase

Question 40

How do macrophages in plaques recruit monocytes?

Answer 40

They express cytokine mediators

Question 41

What do cytokines do in atherosclerosis?

Answer 41

They activate endothelial cell adhesion molecules

Question 42

What do chemokines do in atherosclerosis?

Answer 42

They are chemoattractants | to monocytes

Question 43

Describe how inflammation in atherosclerosis is a positive feedback loop?

Answer 43

Cytokines and chemokine release increases the release of other cytokines and chemokines, so there is a vicious cycle leading to self perpetuating inflammation

Question 44

For what type of cells do macrophages in plaques display chemo attractants and growth factors?

Answer 44

Vascular smooth muscle cells

Question 45

What do vascular smooth muscle cells do once they have been recruited by macrophages in atherosclerosis?

Answer 45

They proliferate and deposit extracellular matrix

Question 46

What states are vascular smooth muscle cells normally and then when they become athersclerotic?

Answer 46

Normally they are contractile, they then become synthetic

Question 47

What causes the change from contractile to synthetic in vascular smooth muscle cells?

Answer 47

PDGF (platelet derived growth factor) and TGF-b (transforming growth factor beta)

Question 48

What does PDGF do?

Answer 48

It causes: VSMC chemotaxis VSMC survival VSMC division (mitosis)

Question 49

What does TGF- beta do?

Answer 49

Increased collagen synthesis | Matrix deposition

Question 50

What happens to contractile filaments and matrix deposition genes when VSMC switch from contractile to synthetic?

Answer 50

Contractile filaments go from high to low in number | Matrix deposition genes go from silent to being upregulated

Question 51

What do proteinases displayed by macrophages in plaques do?

Answer 51

They degrade tissue and plaques, eventually this leads to plaque erosion or rupture (can lead to occlusive blood flow and death)

Question 52

What is an example of a proteinase displayed by macrophages in plaques?

Answer 52

Metalloproteinases

Question 53

What is the lipid necrotic core?

Answer 53

Central death zone where macrophages release tissue factors and toxic lipids

Question 54

What is nuclear factor kappa B?

Answer 54

A transcription factor that is a master regulator of inflammation

Question 55

What is nuclear factor kappa B activated by?

Answer 55

Scavenger receptors Toll-like receptors Cytokine receptors e.g. IL-1

Question 56

What genes does nuclear factor kappa B switch on?

Answer 56

Inflammatory genes eg Matrix metalloproteinases Inducible nitric oxide synthase Interleukin-1