Cholesterol and HDL metabolism

Question 1

What is HDL

Answer 1

Smallest but most dense lipoprotein
Good cholesterol
carries cholesterol from tissue back to liver
excreted in bile
low levels increase risk for heart disease

Question 2

What is reverse cholesterol transport

Answer 2

Pathway that uses HDL to carry excess cholesterol from non-hepatic cells back to the liver for excretion into bile

Question 3

Why is HDL referred to as good

Answer 3

HDL is referred to as “good” cholesterol because it is cholesterol
that is being removed from your body and will not contribute to
atherosclerosis

Question 4

Main organ of cholesterol synthesis and excretion

Answer 4

liver

Question 5

How much cholesterol is excreted per day

Answer 5

1g

Question 6

Step 1 of reverse cholesterol transport

Answer 6

Formation of nascent HDL

Question 7

Step 2 of reverse cholesterol transport

Answer 7

HDL maturation

Question 8

Describe formation of nascent HDL

Answer 8

Derived from liver products
Consists of ApoA1, FR and phospholipid
ABCA1 transfers FC/PC from liver cells to apoA1 for nascent HDL formation
apoA1- forms a belt around the lipid
Nascent HDL functions as a cholesterol acceptor

Question 9

Describe HDL maturation

Answer 9

Maturation of the nascent discoidal HDL to spherical HDL through the actions of LCAT

Question 10

Describe the LCAT reaction

Answer 10

LCAT reaction occurs at the surface of nascent HDL
LCAT binds to apoA1 to become activated
LCAT releases the FA from PC to generate CE
LCAT increases the CE content of HDL

Question 11

t/F HDL contains a lot of other proteins and lipids

Answer 11

true

Question 12

Step 3 of reverse cholesterol transport

Answer 12

Delivery of cholesterol from tissues on HDL to the liver

Question 13

describe the delivery of cholesterol from tissues on HDL to the liver

Answer 13

Uptake of HDL-cholesterol by the liver occurs by scavenger receptor

Uptake of HDL-cholesterol by the liver
produces lipid-poor HDL which recirculate and can pick up more cholesterol from non-liver tissues

Cholesterol from HDL is preferentially excreted into bile into the small
intestine and eliminated in feces

Scavenger receptors have a greater affinity for mature HDL

Question 14

How is LCAT activated

Answer 14

apoA1 binds it

Question 15

How does removing cholesterol from tissues via HDL prevent or reverse atherosclerosis

Answer 15

Increasing cholesterol efflux from macrophages in the artery wall will minimize reduce foam cell formation
Reverse plaque formation (plaque regression)

Question 16

How do you increase HDL levels

Answer 16

Increase HDL levels by:
increasing ApoA1 levels
Increasing LCAT levels
Niacin

Question 17

What is niacin

Answer 17

Vitamin B3 supplement
Precursor for NAD and NADP
Decreases lipid levels
if taken at high doses causes liver damage
Increases HDL cholesterol and apoA1
moderately effective

Question 18

How do you increase cholesterol efflux

Answer 18

Provide more cholesterol acceptors –> more nascent discoidal HDL

Question 19

How do you increase the number of nascent discoidal HDL

Answer 19

Infuse and HDL mimetic

Question 20

what is an HDL mimetic

Answer 20

artificial nascent HDL that doesn’t have free cholesterol

Question 21

What is CER-001? Can it reverse atherosclerosis

Answer 21

drug that stimulates reverse-cholesterol transport

Increased HDL in humans

No plaque regression

Question 22

3 diseases of HDL metabolism? What is the common effect

Answer 22

apoA1
LCAT deficiency
ABCA1-deficiency
Formation of mature HDL is impaired

Question 23

What is familial apoAI deficiency? What is severity dependent on? Diagnosis? treatment?

Answer 23

Mutation in APOA1 gene
less than 1 in 1 million

Depend on the mutation:
1. Mutations that reduce apoA1 levels –> low HDL, milder cardiovascular symptoms
2. Complete apoAI deficiency –> impaired reverse-cholesterol transport, very low HDL, high risk of early-onset atherosclerosis

Diagnosis: xanthomas, premature atherosclerosis, low HDL

Treatment: no cure, Statins can lower blood cholesterol

Question 24

What is Familial LCAT deficiency? Symptoms? Treatment?

Answer 24

Very rare
Single nucleotide mutation resulting in no LCAT activity in plasma
Can’t convert nascent HDL to mature HDL
decreased HDL

Corneal opacity and kidney damage

some develop atherosclerosis

Enzyme replacement therapy: Pure LCAT infusion was safe and well tolerated, however it is not sustained long-term and would need multiple injections