Dyslipidaemia

Question 1

List some of the modifiable risk factors of atherosclerosis

Answer 1

High LDL, low HDL, diabetes, smoking, obesity, high saturated fat intake, etc

Question 2

What determines the stability of an atherosclerotic plaque?

Answer 2

The fibrous cap. Thicker caps are less likely to rupture. Still not good as the lumen will be narrow

Question 3

What is the first stage of atherosclerotic plaque development? This results in the reduced production of which molecules?

Answer 3

Endothelial dysfunction - e.g. endothelial cell injury. Causes the ECs to become compromised. Can cause reduced production of nitric oxide and prostacyclin

Question 4

Once endothelial injury has occurred, the cells express adhesion molecules which promote the attachment of which cells? What happens then?

Answer 4

Promotes attachment and migration of monocytes. These monocytes are then internalised past the membrane, and mature / differentiate into macrophages

Question 5

Foam cells are an important part of atherosclerotic plaques. Explain their development.

Answer 5

Macrophages inside the vascular wall begin to accumulate and together with LDL /cholesterol, they form foam cells. These foam cells increase in number and size, and promote the migration of smooth muscle cells upwards towards the plaque

Question 6

Helpful roles of cholesterol?

Answer 6

Involved in synthesis of bile acid and hormones, important component of cell membrane, and absorbs lipid soluble vitamins from the GIT

Question 7

Define lipoprotein

Answer 7

A vesicle-like structure that carries lipids around the blood.

Question 8

Define apolipoprotein

Answer 8

A protein on the surface of a lipoprotein that is specific for certain receptors. This is what directs the lipoprotein to its target.

Question 9

Name 4 lipoproteins

Answer 9

Chylomicrons, VLDL, LDL, HDL

Question 10

Role of a chylomicron?

Answer 10

Transports dietary lipids from the intestine to the liver and tissues

Question 11

Compare VLDL and LDL

Answer 11

VLDL transports cholesterol and triglycerides from the liver to tissues. LDL is what remains once the VLDL looses its triglycerides

Question 12

Explain the role of HDL

Answer 12

Transports cholesterol back to the liver

Question 13

Explain the role of lipoprotein lipase

Answer 13

Hydrolyses triglycerides into free fatty acids

Question 14

What happens to the chylomicron once the triglycerides have been hydrolysed by LPL?

Answer 14

It gets taken up by the liver, where the cholesterol is stored

Question 15

Causes of low HDL?

Answer 15

Cigarette smoking, anabolic steroids, hiv medications

Question 16

MOA of statins?

Answer 16

HMG-CoA reductase inhibitors. This enzyme is the rate limiting step of cholesterol synthesis, therefore statins reduce cholesterol synthesis.

Question 17

Reduced cholesterol synthesis results in?

Answer 17

Increased LDL receptor expression on hepatocytes and an increased uptake of LDLC from the bloodstream
= reduced plasma LDL-C

Question 18

Fibrates are agonists of which receptor?

Answer 18

PPAR-alpha nuclear receptor

Question 19

Fibrate MOA?

Answer 19

Agonises the PPAR-alpha nuclear receptor which increases transcription of lipoprotein lipase (LPL) and HDL lipoproteins

Question 20

Name 2 fibrates.

Answer 20

Fenofibrate and gemfibrozil

Question 21

Which drug inhibits the absorption of cholesterol in the intestine (duodenum)?

Answer 21

Ezetimibe

Question 22

Which drug class does cholestyramine belong to?

Answer 22

Bile-acid binding resin

Question 23

How do bile acid binding resins work?

Answer 23

They bind to / sequester bile acids in the intestine, which prevents it from being returned to the liver by promoting its excretion. This means the liver needs to use cholesterol to produce more bile acid

Question 24

Compare PCSK9 MABs and siRNA drugs

Answer 24

The MABs bind to the protein and prevent it from degrading LDL receptors, whereas the siRNA drugs silence the transcription of the protein (stopping its synthesis)

Question 25

Which lipoprotein contains the most cholesterol?

Answer 25

LDL

Question 26

Which lipoprotein can easily cross the endothelial barrier?

Answer 26

LDL

Question 27

Function of a liposome?

Answer 27

Breaks from the lipoprotein once it is taken up into a cell to gain access to the cholesterol or triglycerides that are inside

Question 28

HDL is pro-atherogenic. True or false?

Answer 28

False. It is anti-atherogenic.

LDL, VLDL + chylomicron remnants are pro-atherogenic

Question 29

What protein does ezetimibe inhibit in the intestine?

Answer 29

NPC-1L1