Fundamentals of atherogenesis

Question 1

what are the risk factors for atherosclerosis?

Answer 1

Age
Tobacco Smoking
High Serum Cholesterol
Obesity
Diabetes
Hypertension
Family History

Question 2

Why does smoking cause atherosclerosis?

Answer 2

results in damage to the endothelium

Question 3

how does obesity cause atherosclerosis?

Answer 3

fat contains growth factors and is pro-inflammatory

Question 4

What is the distribution of atherosclerotic plaques along the length of an artery?

Answer 4

focal distribution

in areas where there may be turbulent flow eg at bifurcations

Question 5

what is the structure of a plaque?

Answer 5

Lipid
Necrotic core
Connective tissue
Fibrous “cap”

Question 6

What is the key initiating factor in atherosclerosis?

Answer 6

endothelial injury leading to endothelial dysfunction

circulating leukocytes then migrate into the vessel wall

Question 7

When is inflammation goog?

Answer 7

pathogens
parasites
tumours
wound healing

Question 8

Give examples of where inflammation is bad

Answer 8

myocardial reperfusion injury 
atherosclerosis 
IHD
RA 
asthma
IBD
shock

Question 9

How does LDL cause endothelial damage?

Answer 9

LDL passes in and out of the arterial wall and when in XS, it accumulates in the arterial wall and undergoes oxidation and glycation

Question 10

How is adhesion of inflammatory cells brought about?

Answer 10

chemoattractants are released from the injured endothelium and send signals to leukocytes

Question 11

Names some inflammatory cytokines found in plaques

Answer 11

IL-1
IL-6
IL-8
IFN-g
TGF-b
MCP-1 (Monocyte chemoattractant protein)
C reactive protein

Question 12

Which cytokine induces the production of the other cytokines?

Answer 12

IL-1

Question 13

Which adhesion molecule facilitates capture and rolling of leukocytes?

Answer 13

selectins

Question 14

Which adhesion molecule facilitates firm adhesion of leukocytes?

Answer 14

integrins

Question 15

What is the name given to the earliest lesion of atherosclerosis?

Answer 15

fatty streaks

Question 16

what do fatty streaks consist of?

Answer 16

lipid laden macrophages
T cells
within the intima

Question 17

What is the next stage of plaque formation after fatty streaks?

Answer 17

intermediate lesions

Question 18

What do intermediate lesions consist of?

Answer 18

lipid laden macrophages - foam cells 
vascular smooth muscle cells 
T cells 
platelets 
extracellular lipid

Question 19

What is the next stage of plaque formation after intermediate lesions?

Answer 19

fibrous plaques / advanced lesions

Question 20

What is the definitive feature of fibrous plauqes?

Answer 20

covered by a fibrous cap

Question 21

What is a fibrous cap made of and how is it made?

Answer 21

collagen
elastin
made by SMCs that overly the lipid core and necrotic debris

Question 22

What is a fibrous cap made of and how is it made?

Answer 22

collagen
elastin
may be calcified
made by SMCs that overly the lipid core and necrotic debris

Question 23

What is a fibrous plaque made of?

Answer 23

fibrous cap
smooth muscle cells
foam cells
T cells

Question 24

What is the difference between the fibrous cap of stable angina and unstable angina?

Answer 24

the fibrous cap of stable angina plaque is much weaker

Question 25

What is the pathogenesis behind plaque rupture?

Answer 25

the plaque is constantly growing and receding and the fibrous cap has to be resorbed and redeposited to be maintained if the balance is shifted in favour of increased enzyme activity (matrix metalloproteases), the cap becomes weak and ruptures

Question 26

What causes thrombus formation when a plaque ruptures?

Answer 26

exposure of BM, collagen and necrotic tissue | haemorrhage of blood vessels in the plaque

Question 27

Name two commonly used drugs in drug eluting stents

Answer 27

Sirolimus = rapamycin - immunosuppresant and anti-proliferative Taxol - inhibits cell growth of neointima

Question 28

What are the four major cell types involved in atherogenesis?

Answer 28

``` endothelium macrophages smooth muscle cells platelets ```