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Fat, cholesterol, and atherosclerosis

29 important questions on Fat, cholesterol, and atherosclerosis

How does a myocardial infarct or stroke occur?

There is a clot in a coronary artery, therefore the heart does not get enough oxygen. This leads to tissue damage, the heart muscle dies and scar tissue is formed. Which in the end leads to loss of function of the heart.

What is a prevention of getting a heart attack when you have clogged a artery?

The dotter procedure. During surgery a balloon with a stent will go into the artery. The balloon is blown up and the stent stays in the artery. The artery is open again now.

Triglycerides are high in which lipoproteins?

Chylomicrons, VLDL, and HDL

What happens to the fats in your diet?

The triglycerides are packaged in chylomicrons and via the lymph they go into the blood so they can be used as fuel by the muscle and adipose tissue. They are released again by lipase. FA go into the tissues or are stored. Remnants of the chylomicrons go back to the liver to be recycled.

What happens to fats in between diets or when you're on a fat free diet?

You have a lot of carbohydrates and you make new fat from this. These are packaged in VLDL and transported to the tissue to use but also to the adipose tissue for storage. When the triglycerides are being taken out, the cholesterol remains and the density becomes somewhat denser. Now we call it LDL. LDL will be recycled in the liver.

What is the difference between the LDL and chylomicron protein?

They both use the same gene for their protein: the B-apoprotein gene. The protein for LDL is the ApoB-100. This is the full protein. The protein for chylomicron is the ApoB-48. This one is edited in the liver, so it's not the full size.

What is forward (cholesterol) transport?

Triglyceride delivery to the tissues. Transports cholesterol to the tissues. Chylomicrons, VLDL, and IDL have a lot of this triglyceride in them.

How are atherosclerotic plaques formed?

Cholesterol (LDL) passes through the tunica intima and gets oxidized into OxLDL. This is seen as a foreign particle and immune cells are recruited. The macrophages eat the OxLDL but they cannot degrade them completely, this leads to foam cells. This leads to more inflammation and in the end plaque formation.

The macrophages have special receptors for OxLDL. What are these called?

E36 and LOX1, these are the so-called scavenger receptors.

What are metalicmetalproteases (MMPs)?

These are cleavage enzymes that are released by signalling molecules that are activated by the inflammation of the atherosclerotic plaques. These enzymes try to cleave the fibrotic cap. However, in the end this only leads to rupturing of the cap and you get vessel damage, leading to clotting and a real occlusion of the vessel.

What can happen to the vessel wall if you have a lot of inflammation (because of an atherosclerotic plaque)? What happens next?

It can rupture. When it ruptures a real thrombus will form trying to heal the rupture. This thrombus leads to the real occlusion.

What is the function of HDL particles?

Bring the cholesterol from the tissue to the liver, to be recycled.

Which lipoprotein is associated with HDL particles?

ApoA1, the L178P.

What happens if you have a mutation in the ApoA1?

You have very low HDL particles, leading to a higher chance of dying from a heart attack.

Why is it better to look at the ratio LDL/HDL? What is better: high or low ratio?

Low HDL cholesterol increases chance of getting heart disease, even when the LDL cholesterol is low. Therefore, you should look at the LDL/HDL ratio. The lower the ratio, the better.

What are the changes associated with insulin resistance?

Lipoproteins:

Increased ApoB (LDL will increase)
Decreased ApoA1 (HDL will decrease)
Small dense LDL and HDL
Increased ApoC3 (more chylomicrons)

LDL/HDL ratio will increase.

What is the consequence for your liver of having a high amount of fat in your diet?

When your diet contains a high amount of fat, your fat organs will become inflamed. Fat organs are endocrine organs and they secrete hormones and cytokines. When the fat organs get inflamed they induce an inflammatory reaction. In the end you see that these people make so much fat that they cannot even transport it to the tissues anymore and it starts to accumulate in the liver. This is called non-alcohol fatty liver disease (NFLD).

What is a better way to predict the chance of getting heart disease than looking at cholesterol levels?

C-reactive protein

Not 100% of the cholesterol is ingested through the diet. What is done to get to 100%?

Approximately 80% is not ingested, this is made by the liver.

What have companies done when they say they can lower cholesterol levels?

They say that they can coagulate bile salts, preventing them to be reabsorbed. In this way your bile salts will be secreted via your feces. However, the bile salts (cholesterol) that is lost, is just made again by the liver, so this doesn't really work.

What is familial hypercholesterolemia?

These people have accumulations of cholesterol in the skin. This is because they have a problem with their LDL receptor. Their LDL receptor doesn't work so they keep making cholesterol, even though they already have enough.

How does cholesterol regulate its own synthesis?

The sterol regulatory element-binding protein (SREBP) is being kept together when there is enough cholesterol. When you don't have enough cholesterol it is not bound to the complex anymore and the DNA binding element goes to the nucleus to induce gene transcription.

What is the mechanism of statins?

Statins are competitive inhibitors of HMG-CoA reductase. In this way you prevent the HMG-CoA to bind and prevent synthesis to occur. You only need to block the production that is too much (that is why we use a competitive inhibitor). You need much more of the HMG-CoA to compete out the statin.

You can make different types of FA, except for 2. Which one?

Omega-3 and omega-6

One of the most important enzyme of eicosanoids is?

Cyclooxigenase. There are two versions: COX1 and COX2.

What is the mechanism of aspirin (and other painkillers)?

Aspirin blocks COX1 and COX2 to prevent the synthesis of the local signalling molecules (like the prostaglandins).

What happens if you only block COX2 (since only this one is induced by inflammation)?

COX1 and COX2 have opposite effects. COX1 makes TXA2 which promotes platelet aggregation. COX2 prevents this platelet aggregation. So if you would only block COX2 the platelets would aggregate and this would lead to a thrombosis.

There have been some drugs that block COX2. What is the name of these?

Coxibs

What is the mechanism of glucocorticoids?

Glucocorticoids block the arachidonic acid pathway but they block the formation of arachidonic acid. Therefore, they also block immune responses.

The question on the page originate from the summary of the following study material:

Medical Biochemistry

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