Pharm 17 - Lipoproteins And Atherosclerosis

Front 1

What is a Chylomicron?
Where does it come from?

Back 1

a droplet of fat present in the blood or lymph after absorption from the small intestine

Front 2

What is LP lipase?
What does it do?

Back 2

Lipoprotein lipase
Hydrolyses TIRGLYCERIDES in VLDL and chylomicrons to leave FATTY ACIDS + GLYCEROL

Front 3

What are the dangers of plaque rupture?

Back 3

Sudden release of pro-thrombotic material - all the lipid and inflammatory mediators

Front 4

What are the different lipoproteins?
(4)

Back 4

Chylomicron
VLDL
LDL
HDL

Front 5

What do chylomicrons carry?
Where from?
Where to?

Back 5

DIETARY Cholesterol and a fuckton of triglyceride from the small intestine

Front 6

What do VLDLs carry?
Where from?
Where to?

Back 6

Cholesterol and triglyceride synthesised in the LIVER
To adipose tissue+other cells

Front 7

What do LDLs carry?
Where from?
Where to?

Back 7

Cholesterol and triglyceride synthesised in the LIVER
To body cells

Front 8

What do HDLs carry?

Where from?
Where to?

Back 8

Cholesterol +protein
From body
To liver

Front 9

Generally speaking what is the function of the lipoproteins?

Back 9

To move cholesterol and lipid to where it is needed in the body

Front 10

What are chylomicron remnants?

Back 10

Leftover bits of chylomicron

Front 11

Where are the chylomicrons meant to end up?

Back 11

Meant to end up in the liver, with their contents processed and resynthesised into useful things

Front 12

Why do chylomicrons/LDLs interact with blood vessel wall?
Which layer do they accumulate in?

Back 12

Endothelium is damaged and so becomes "sticky"

They move into the intima layer

Front 13

What happens after LDL/chylomicrons first accumulate in intima?

Back 13

Macrophages ingest them and become foam cells

Front 14

What happens after foam cell development?

Back 14

Foam cells cannot digest fat, so emit cytokines

Front 15

What happens after foam cells emit cytokines?
(Cytokines -- INFLAMMATION)

Back 15

Monocytes from blood are recruited
T cells
Smooth muscle cells differentiate
Platelets

Front 16

What aspects of atherosclerosis does this quote refer to: "atherosclerosis is an inflammatory fibroproliferative disorder"?

Back 16

Inflammatory: the mast cells and the foam cells

Fibroproliferative: calcification of plaque sclerosis of vessel

Front 17

Describe the features of an unstable plaque

Back 17

Necrotic lipid core
Thin fibrous, calcified cap
Shape of protrusion into lumen

High inflammatory activity
Haemorrhage within plaque

Front 18

What is inside the plaque which is thrombogenic?

Back 18

Tissue factor
Platelet aggregating factors(?)

Front 19

What tests exploit the calcification of plaques in diagnosis/predicting prognosis?

Back 19

Cardiac CT
Calcium levels predict extent of calcification of plaque, higher calcium means more unstable plaque
(controversial)

Front 20

What lifestyle things are risk factors for high LDL?
Low HDL

Back 20

Smoking
High triglyceride diet
Lack of physical activity

Front 21

What level of serum triglyceride is assosciated with atheromae risk?

Back 21

>1000mg/dl

Front 22

Modified vs unmodified VLDL/chylomicron is what?

Back 22

Modified is worse

Front 23

Why do we want to reduce serum cholesterol?

Back 23

10% cholesterol reduction gives 11 % reductoin of CVS mortality

Front 24

How do bile acid sequestrants work?

Back 24

They bind to bile acids, prevents absorption of the cholesterol
However it stimulates cholesterol synthesis

Front 25

How do statins work?

Back 25

Inhibits HMG-CoA reductase which is rate-limiting step in melavonate synthesis in liver
Liver does not make cholesterol
Cholesterol is needed to make other things (e.g. GPP and FPP)
LDL-receptors on liver cell is upregulated in orer to absorb more LDL

Front 26

What is the HMG-CoA reductase pathway really for?

Back 26

Synthesis of mevalonate/ also farnesyl pyrophosphate and geranyl pyrphosphate

Front 27

What do farnesyl pyrophosphate and geranyl pyrophosphate do?

Back 27

Post translational modification of rho and ras proteins

NB RAS protein is the intracellular-bound G-protein which is activated by sos

Front 28

How does the liver respond to lack of cholesterol synthesis?

Back 28

Puts out more LDL receptors on its surface

Front 29

When applying the term "selectivity" for statins, what type of cell do we want the statin to be selective for?

Back 29

Liver

Front 30

Which statin is better at reducing cholesterol?
Rosuvastatin or simvastatin

Back 30

Rosuvastatin (50%)

Front 31

What is the Rule of Six?

Back 31

Increasing a dosage of any statin by 2fold, will always increase cholesterol production by only an absolute 6%

Front 32

What pleiotropic effects of statins?

Back 32

Anti-inflammatory
Actually used in arthritis

Front 33

How do fibrates work?

Back 33

They activate the PPARs
PP alpha receptor

Front 34

What do they do?

Back 34

They lower blood triglycerides and fatty acids
And increase HDL
Nothign to LDL

Front 35

Nicotinic acid/niacin

Front 36

Ezetimibe

Back 36

Converted in body to gluconiride

Front 37

How does Ezetimibe work?

Back 37

Stops cholesterol drom being absorbed

Front 38

How is ezetimibe used in clinical practice?

Back 38

Topping up statins

Front 39

What is CETP
What does it do?

Back 39

Cholesterol ester transfer protein
Converts HDL to LDL

Front 40

CETP inhbitors did what positively?
Did what badly?

Back 40

Increased HDL levels and lowerd LDL levels
Possiblky raised blood pressure

Front 41

PCSK9 is what?

Back 41