Artherosclerosis

Question 1

What is atherosclerosis overview?

Answer 1

Low grade inflammatory damage to arteries leads to plaque formations
These can rupture and trigger blood clots

Question 2

What are foam cells?

Answer 2

Mostly macrophages

Question 3

How do plaques form?

Answer 3

Foam cells take up lots of lipids and accumulate within plaques
Some may get stressed and die and some may not get taken up by other cells, so you get fat deposits and lesions

Question 4

What is a complicated lesion

Answer 4

One which has ruptured

Question 5

Where do you tend to get development of plaques?

Answer 5

At bifurcation

Question 6

Why do you get development of plaques at bifurcation?

Answer 6

Turbulent blood flows affect the cells

Question 7

What are environmental/life cycle risk factors for atherosclerosis?

Answer 7

Smoking
Obesity
Diet
Diabetes
Hypertension
Alcohol excess
Exercise
Age
Periodontal infections

Question 8

What are genetic risk factors for atherosclerosis?

Answer 8

Apolipoprotein E - a key component of VLDL
High CRP
Diabetes
ApoA-I deficiency - low HDL levels
LDL receptor mutations - familial hypercholesterolaemia
Being male

Question 9

What are inflammatory triggers for atherosclerosis?

Answer 9

Oxidation of self molecules
Oxidative damage to LDL and lipids

Question 10

What is the initiation stage of atherosclerosis?

Answer 10

Cell migration

Question 11

What happens in the initiation stage of atherosclerosis?

Answer 11

Change in turbulent flow
Increased transcytosis of LDL and oxidative changes
Increased VCAM/ICAM/selectins
Cytokine secretion
Recruitment of monocytes and T cells

Question 12

What happens in early development of atherosclerosis?

Answer 12

Local production of M-CSF+
Monocytes differentiate to macrophages
Increase macrophages, TLRs etc.
TLR4 (+) activation by ox-LDL components
NFkappaB, MAPK activation
Pro-inflammatory responses

Question 13

What happens in progression to plaque stage?

Answer 13

Accumulation of foam cells
T cells bias to Th1 response
Local antigen presentation by macrophages
Plasticity of SMC > macrophage like and osteocyondrocyte like cells

Question 14

What happens in an excess of cholesterol to bone marrow?

Answer 14

If you have an excess of cholesterol it can push cells in the bone marrow to produce more macrophages and monocytes etc.

Question 15

What normally happens with the unused flow of lipids in the form of LDL?

Answer 15

Normally are delivered into tissues and what isn’t used is delivered up from cells and delivered back to the liver through HDL

Question 16

What happens to unused lipids in the form of LDL in atherosclerosis patients?

Answer 16

There is a lot of disruption to pathways
There is an increase in LDL uptake triggered foam cells and decrease levels of receptors you need to handle HDL and pass that lipid back out of the cell
Macrophages become less good at giving up lipids they’ve taken up

Question 17

What are therapeutic interventions for atherosclerosis?

Answer 17

Stents and angioplasty

Question 18

What statins can be used?

Answer 18

HMG-CoA reductase inhibitors (it is one of the starting points of our body making cholesterol)

Question 19

What do peroxisomes-proliferator-activated receptor (PPAR) ligands do?

Answer 19

Inhibit T cell activation, reduce IFNgamma, inhibit SMC activation

Question 20

What do ACE inhibitors do?

Answer 20

Relates to hypertension in blood vessels

Question 21

What is the problem with anti-TNF biologics, IL-1 blockage, IL-1 blockage with antibodies?

Answer 21

Very good at doing their job but they are very expensive

Question 22

What could a potential vaccine target for atherosclerosis?

Answer 22

Target molecules which downregulate liver LDL clearance (such as PCSK9)