Lipid transport and statins

Question 1

Describe plaque formation in CVD

Answer 1

damaged endothelial cells provide sites for accumulation of fats
fatty streaks signal for recruitment of immune cells
macrophages eat cholesterol and turn into foam cells in plaque
smooth muscle cells grow into the plaque generating fibrous cap
plaque reduces blood flow
necrosis at core can cause plaque rupture and thrombus formation, blocking arteries

Question 2

Name the 3 types of lipids in our bodies

Answer 2

triglyceride
phospholipid
steroid

Question 3

What type of lipid is cholesterol?

Answer 3

steroid

Question 4

What do we need cholesterol for?

Answer 4

used to make steroid hormones and bile salts

increases cell membrane fluidity

Question 5

What makes lipids insoluble in aqueous solutions?

Answer 5

hydrophobic tails

Question 6

Describe the structure of lipoproteins

Answer 6

phospholipid shell - polar head groups

hydrophobic lipid core

apolipoprotein - hydrophobic domain binds lipid, hydrophilic domain targets particle

Question 7

What is the major source of cholesterol in the body?

Answer 7

diet

Question 8

Where are bile salts produced and what do they do?

Answer 8

produced in liver by chemically modifying cholesterol
act as detergents to assist in absorption of insoluble cholesterol from the intestine

Question 9

Describe how cholesterol is packaged to travel in the blood

Answer 9

cholesterol (in complexes with bile salts) is taken into intestinal epithelium, esterified and packaged into lipoprotein particles for transport in the blood

Question 10

What is LDL a measure of?

Answer 10

cholesterol headed to tissues

Question 11

What is HDL a measure of?

Answer 11

cholesterol headed to liver for excretion via bile salts

Question 12

Name a anti-atherogenic lipoprotein

Answer 12

HDL (high density lipoprotein)

Question 13

Name some pro-atherogenic lipoproteins

Answer 13

chylomicrons
VLDL
LDL
IDL

Question 14

Normal LDL level

Answer 14

70-130 mg/dL (lower the better)

Question 15

Normal HDL level

Answer 15

40-60 mg/dL (higher the better)

Question 16

What is familial hypercholesterolaemia?

Answer 16

genetic disease characterised by high cholesterol and LDL in blood

Question 17

Familial hypercholesterolaemia inheritance

Answer 17

single gene
autosomal dominant transmission
defective/absent LDL receptor

Question 18

Familial hypercholesterolaemia symptoms

Answer 18

xanthoma - yellowish lipid deposits around eyelids, and lumpy deposits in tendons of the hands, elbows, knees and feet

Question 19

Statins MOA

Answer 19

HMG-CoA reductase enzyme inhibitors
(this enzyme catalyses the rate-limiting step in cholesterol synthesis in our cells)

leads to increased levels of LDL receptor so more LDL particles are taken up into cell and hence cholesterol levels in the blood fall

Question 20

Describe hoe HMG-CoA reductase gene is involved in negative feedback

Answer 20

product inhibition
expression of HMG-CoA reductase gene is inhibited by the eventual product of its activity

product (cholesterol) inhibits more synthesis

Question 21

Is cholesterol in cells damaging?

Answer 21

no
it is cholesterol in blood that promotes atherosclerosis

Question 22

How can plant sterols (eg. benecol) lower cholesterol uptake from the diet?

Answer 22

they compete with cholesterol for binding to transporters

Question 23

Ezetimibe MOA

Answer 23

blocks NPC1L1 (Niemann-Pick C1-Like 1)
NPC1L1 = increases uptake of cholesterol from the diet