Atherosclerosis and Lipometabolism Flashcards

1
Q

What is the main difference in the composition of LDLs and HDLs?

A

They have different apoproteins

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2
Q

What are dietary triglycerides and cholesterol packaged into once they are absorbed?

A

Chylomicrons

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3
Q

What are chylomicrons broken down into?

A

Chylomicron remnants

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4
Q

Are most circulating lipids endogenous or exogenous?

A

Endogenous

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5
Q

What is the significance of chylomicron remnants with regards to atherosclerosis?

A

They are very good at getting into the tunica intima

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6
Q

Define atherosclerosis.

A

Atherosclerosis is an inflammatory fibro-proliferative disorder

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7
Q

What cells are recruited in the process of atherosclerosis?

A

Macrophages (which turn into foam cells)
Fibroblasts
Smooth muscle cells

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8
Q

What must initially happen for the process of atherosclerosis to begin?

A

Increase in permeability of the endothelium Upregulation of leukocytes and cell adhesion molecules
Migration of leukocytes into arterial wall

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9
Q

What can happen as the atheroma grows larger?

A

Some of the foam cells die and rupture, releasing their toxic contents to form a lipid necrotic core

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10
Q

Which cells are responsible for producing a protective fibrous cap over the fat core?

A

Smooth muscle cells lay down collagen fibres

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11
Q

What is an unstable atherosclerotic plaque?

A

The fibrous cap thins and eventually ruptures, exposing the thrombogenic lipid core to the platelets and coagulation factors This causes THROMBOSIS

NOTE: plaque erosion is also associated with hardening of the arteries, leading to weakening and thickening of the vessel wall leading to aneurysm and possible haemorrhage

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12
Q

What do complicated lesions often contain?

A

Calcium

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13
Q

What are some characteristics of vulnerable plaques?

A

Thin fibrous cap
A core rich in lipid and macrophages
Less evidence of smooth muscle proliferation

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14
Q

What can modify LDL cholesterol?

A

Low HDL
Diabetes
Smoking
Hypertension

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15
Q

What do low HDL cholesterol levels tend to be associated with?

A

High triglyceride levels

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16
Q

What factors can lower HDL cholesterol levels?

A

Smoking
Obesity
Physical inactivity

17
Q

What is considered a normal triglyceride level?

A

< 200 mg/dL or 2.3 mmol/L

18
Q

Other than heart disease, what else is a very high triglyceride level associated with?

A

Pancreatitis

19
Q

State some different drug therapies that have been used to treat high cholesterol.

A

Bile acid sequestrants
Nicotinic acid
Fibrates
Statins

20
Q

Describe the mechanism of action of statins.

A

They are HMG-CoA reductase inhibitors

21
Q

What are two important products of the cholesterol synthesis pathway?

A

Geranyl pyrophosphate
Farnesyl pyrophosphate

They are involved in the modification and activation of proteins

22
Q

How do statins decrease plasma LDL levels?

A

Statins block the cholesterol synthesis pathway, which leads to the liver responding by producing more LDL receptors

Having more LDL receptors means that more LDL can be removed from the blood

23
Q

What is the selectivity ratio of a statin?

A

The higher the selectivity ratio, the greater the likelihood of the molecule being concentrated in the liver cell

24
Q

What is the Rule of 6?

A

Doubling the dose of any statin will give a 6% reduction in the level of LDL cholesterol

25
Q

How do fibrates act?

A

They activate PPAR-alpha They lower plasma fatty acids and lower triglycerides They are often used in diabetics with high triglycerides

26
Q

Name an important drug that can be given with statins to further decrease LDL levels?

A

Ezetimibe – it inhibits cholesterol absorption

27
Q

What is this drug activated as?

A

Glucuronide

28
Q

Which protein is involved in the transport of cholesteryl esters and triglycerides from HDLs to LDLs?

A

Cholesteryl Ester Transfer Protein (CETP)

29
Q

What was the result of attempted inhibition of CETP?

A

It increased HDL and decreased LDL but it had off target effects that led to increased mortality

NOTE: the drug was called torcetrapib

30
Q

What is PCSK9?

A

It is an inhibitor of LDL receptors It stops the LDL in the plasma from binding to the LDL receptor and being taken up PCSK9 inhibition can lead to a decrease in cholesterol levels