Atherosclerosis

Question 1

How does hypertension increase changes of atherosclerosis?

Answer 1

leads to a higher chance of endothelial injury due to greater pressure within the aorta e.g. aneurysm

Question 2

How does impaired glucose tolerance lead to higher chance of atherosclerosis

Answer 2

more circulating glucose –> lipoproteins leading to greater risk of atheroma

Question 3

How does age lead to increased risk of atherosclerosis?

Answer 3

thickening & hardening of artery walls

Question 4

How does gender affect chances of developing atherosclerosis?

Answer 4

women > male esp. post menopause

Question 5

How does hyperlipidaemia lead to increased chances of atherosclerosis

Answer 5

high LDL, carry cholesterol to body cells from liver

Question 6

How does alcohol lead to increased chances of atherosclerosis?

Answer 6

increased risk of ischaemic heart disease (IHD) - fatty liver

Question 7

How does apolipoprotein E genotype lead to increased chances of atherosclerosis?

Answer 7

linked to LDL levels

Question 8

How does familial hyperlipidaemia lead to atherosclerosis?

Answer 8

genetic, early development of atheroma

Question 9

How does haemodynamic stress lead to atherosclerosis?

Answer 9

Means that certain areas of body are more likely to develop atheroma

Question 10

How does infection increase the chances of atherosclerosis?

Answer 10

e.g. chlamydia: secretes cytokines & cause inflammatory response to endothelial cell injury

can also be caused by helicobacter pylori & cytomegalovirus

Question 11

What are the epidemiology of atherosclerosis?

Answer 11

smoking, hypertension, impaired glucose tolerance, age, gender, hyperlipidaemia, alcohol, apolipoprotein E genotype, familial hyperlipidaemia, haemodynamic stress, infection

Question 12

What are the preventions of atherosclerosis?

Answer 12

stop smoking, decrease fat intake, treat hypertension, aspirin, sensible alcohol intake, regular exercise & control of weight, treat D.Mellitus, Lipid lowering drugs where needed

Question 13

How does stoping smoking prevent atherosclerosis?

Answer 13

prevents endothelial damage from the toxins in cigarettes

Question 14

How does decreasing fat intake prevent artherosclerosis?

Answer 14

reduce LDL & cholesterol circulating

Question 15

How does treating hypertension prevent atherosclerosis?

Answer 15

prevents aneurysm

Question 16

How does taking aspirin help prevent atherosclerosis?

Answer 16

prevent aneurysm

Question 17

How does sensible alcohol intake prevent atherosclerosis?

Answer 17

prevents liver damage (fatty liver) prevent atheroma through LDL circulating or blocking function of liver

Question 18

How does regular exercise & control of weight prevent atherosclerosis from forming?

Answer 18

reduce cholesterol

Question 19

How does treating D.M. prevent atherosclerosis?

Answer 19

lower levels of circulating glucose & lipids

Question 20

How does lipid lowering drugs where needed prevent atherosclerosis?

Answer 20

prevent accumulation - preventing formation of atheroma

Question 21

How does smoking increase the chances of atherosclerosis?

Answer 21

toxins from cigarette smoke can lead to endothelial injury

Question 22

What are the cells involved in atherogenesis?

Answer 22

endothelial cells: line arteries, altering permeability to lipoproteins
platelets: aggregate, migration of SM cells (PDGF)
SM cells: take up LDL –> foam cells (collagen synthesis)
Macrophage: become foam cells
Neutrophils: secrete proteases (break down proteins) –> continued local damage + inflammation

Question 23

What is the monoclonal hypothesis?

Answer 23

1 smooth muscle cell gives rise to all smooth muscle cells

Question 24

What is the lipid oxidation hypothesis?

Answer 24

antioxidants help prevent atherosclerosis

atherosclerosis is from oxidative damage from oxidised LDL - inhibited by antioxidants

Question 25

What is insudation hypothesis?

Answer 25

LDL is taken up endothelial cells (receptor mediated) and transcytosed into CT underneath and taken up by macrophage (foam cell)
so when there is endothelial damage, inflammation leads to increased permeability of lipid from plasma

Question 26

What is the encrustation hypothesis?

Answer 26

SM cells react to thrombi + lipids that aren’t associated with vessel walls
(mural thrombi (not in contact with vessel walls) is organised to lead to formation of plaques)

Question 27

What causes and what happens when there is endothelial damage?

Answer 27

hypercholestrolaemia leads to endothelial damage
plaques form in response
injury increases permeability - allowing platelet adhesion
monocytes penetrate endothelium to become macrophage
SM cells prolife + migrate

Question 28

Response to injury hypothesis

Answer 28

SMC proliferation induced by growth factors e.g. PDGF
repetitive injury to endothelial cells lead to release of GF
GF stimulates inflammatory cells + macrophage + SM cells to release more GF
leading to increased SM cell proliferation –> atherosclerosis

Question 29

What is the unifying hypothesis to atherosclerosis?

Answer 29

endothelial injury –> platelet adhesion, releasing platelet derived growth factor, SMC prolife + migrate, becomes foam cells (taken up oxidised LDL), foam cells secrete cytokines, leading to further SMC stimulation (prolife + migrate) and recruitment of other inflammatory cells
monocytes migrate to intima, SMC produce matrix