Bad cholesterol and good cholesterol

Where does cholesterol come from?

The cholesterol in your body comes from two sources: your diet and what you make yourself. Typically, around seven times more cholesterol is made in your body from dietary saturated fats (animal and dairy fat) than is absorbed as cholesterol from your food.

Most cholesterol is made in your liver, but small amounts are also made in almost all other cells in the body, particularly those found in the intestines, adrenal cortex and skin. Your liver can provide all the cholesterol that your body needs, so cholesterol is not an essential part of your diet.

Dietary cholesterol is absorbed from your small intestines, and travels in the blood to your liver, where it mixes with cholesterol produced in the liver itself. Cholesterol from these two sources then travels to other body tissues where it is needed to make cell membranes, and to act as a building block for making steroid hormones or vitamin D.

The role of lipoproteins

As cholesterol does not dissolve in blood serum, which is mostly water, it is first stabilised for transportation. This is done by packaging it in particles called lipoproteins. Lipoproteins are made up of:

• cholesterol and triglycerides (which both need to be transported around the body)
• specialised proteins called apolipoproteins (sometimes shortened to apoproteins or apos)
• phospholipids.

The phospholipids act as detergents which dissolve fats, whereas the proteins help to make the particles stable. It is in this form that cholesterol and triglycerides are transported around the body.

There are five main types of plasma lipoprotein, all of which have slightly different functions and which get their names from their relative density (size and weight) – see the box on page 28.

The two types that are most important for cholesterol transport are low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Most of the cholesterol in blood is in LDL particles – there are more HDL particles than LDL, but HDL particles contain relatively more protein and less cholesterol in each particle.

Lipoproteins and their functions

There are five main types of lipoprotein, all of which have slightly different functions.

Chylomicrons

Made in the small intestine; carry dietary fatty acids directly from the gut to the liver and peripheral tissues where it will be used or stored as fuel
 

Very-low-density lipoproteins (VLDLs)

Made in the liver; carry excess fatty acids from the liver to adipose tissue (fat tissue), where free fatty acids are released and taken up by fat cells for storage
 

Intermediate-density lipoproteins (IDLs)

Made from VLDLs after free fatty acids are released; taken up by the liver and converted into LDL particles
 

Low-density lipoproteins (LDLs)

The main carrier of cholesterol, taking it to peripheral tissues with excess returning to the liver
 

High-density lipoproteins (HDLs)

Made in the liver and intestines; collect cholesterol from cell membranes in peripheral tissues and transport it back to the liver for processing (reverse cholesterol transport)

Cholesterol transport around the body

To body tissues

The liver is the central organ for handling cholesterol. It makes and prepares cholesterol for transport to other organs. Cholesterol and triglycerides are packaged together into very-low-density lipoprotein (VLDL) particles. These particles reach the bloodstream and are carried around your body.

The triglycerides are removed as VLDL passes through organs, and their fatty acids are used as energy for muscles or stored to create energy reserves in adipose (fat) tissue. The VLDL particles become smaller as triglycerides are removed and change into LDLs. As triglycerides have been removed, LDLs are rich in cholesterol.

Locks and keys

The purpose of LDL is to deliver cholesterol to body tissues. Tissues have small pits in their cell walls (LDL receptors), which can be thought of as locks. LDL particles have a special protein on their surface called apoprotein B (or apoB). This is the key that opens the lock of the cell receptors. When the key fits into the lock, the door opens and LDL particles pass into the cell.

Once inside, LDL particles dissolve, releasing the cholesterol that they contain, thus supplying the cells’ needs. Most of the cells’ cholesterol requirements are met in this way, although cells can also manufacture cholesterol when LDL particles cannot get into cells (for example, in familial hypercholesterolaemia).

From body tissues

Cholesterol is continually removed from cells in high-density lipoproteins (HDLs), which take cholesterol from cells to the liver; this then excretes it in the bile. Thus, as well as producing cholesterol, the liver can also remove cholesterol from the blood. Excess cholesterol from cells can be removed from the body by this mechanism.

Lipoproteins and CVD

LDL is sometimes thought of as containing bad cholesterol whereas HDL is regarded as carrying good cholesterol. This is because of the different associations between CVD (cardiovascular disease) and blood levels of these lipoproteins.

LDLs and CVD

The link between high blood cholesterol levels and CVD was outlined on page 12, and it is the cholesterol in LDLs that is responsible for causing atherosclerosis. If LDL-cholesterol levels are high, they are not all removed from the blood by the lock-and-key mechanism outlined earlier. LDL particles find their way through artery walls where they are taken up by macrophages.

Macrophages are scavenger cells that mop up excess particles, such as LDLs, as well as micro-organisms and worn-out proteins. When full of cholesterol these scavenger cells start the process that leads to the development of atherosclerotic plaques and arterial disease. Thus, high LDL levels are bad for health.

HDLs and CVD

Increasingly high blood levels of HDLs are associated with lower risks of developing CVD, hence the view that HDLs contain good cholesterol. The reasons for this are not absolutely clear, but possibly relate to the fact that HDLs remove cholesterol from cells and carry it to the liver. HDLs might therefore prevent cholesterol building up in key sites such as arterial walls, lessening the risk of atherosclerosis.

HDL and antioxidant activity

A further possibility for the protective effects of HDL is that it has antioxidant activity. Oxidation of LDL is thought to occur before the particles are taken up by macrophages in arterial walls, and there is some evidence that antioxidants may prevent this change occurring in LDL particles, and protect against the development of atherosclerosis. Thus, the protective effect of HDL against CVD could be the result of it preventing oxidation of LDL, rather than removing excess cholesterol from cells. It has also been suggested that HDL protects the cells that line the walls of arteries.

Triglycerides and CVD

There is more controversy about a link between raised blood triglyceride levels and CVD than there is for cholesterol. The main reason for this is that the results of clinical studies of triglycerides and CVD have been inconsistent. A further complication is that the levels of LDLs and HDLs are usually affected if blood triglycerides are high. Despite uncertainties, the link between high blood levels of triglycerides and CVD is clearer in women than in men and is also seen in diabetes. This is discussed more fully later.

Very high levels of blood triglycerides increase the risk of developing an inflammation of the pancreas, pancreatitis.

KEY POINTS

• Some cholesterol comes from your diet, but most is made in your body – mainly in liver cells

• Cholesterol is carried in your blood around your body in particles called lipoproteins

• High LDL levels are associated with CVD

• High HDL levels seem to protect against CVD