Why Lipoproteins Are Important

What they are, and what they do

LDL cholesterol
Low Density Lipoprotein. JOHN BAVOSI/Getty Images

Lipoproteins are complex particles, consisting of proteins and fats, that circulate in the bloodstream. The chief purpose of lipoproteins is to transport lipids - mainly cholesterol and triglycerides - from place to place through the bloodstream, and to facilitate the processing of these lipids in the various tissues of the body.

Lipoprotein disorders are strongly associated with the development of atherosclerosis, and thus, with coronary artery disease (CAD), stroke, and peripheral vascular disease.

What Are Lipoproteins?

Lipids are critical to life. Lipids are needed for energy, for the formation of membranes in every cell in the body, for the production of critical hormones (including cortisol and the sex hormones), for bile acids, and for the normal function of the nervous system. So getting the right lipids to the right place at the right time is an important function of all animal life.

However, lipids are insoluble - they do not dissolve in water. So transporting lipids efficiently requires them to be "packaged" in such a way that they can flow through the bloodstream. This packaging is done by the lipoproteins.

Lipoproteins are essentially tiny “containers” which contain lipids. They emulsify the lipids, allowing them to be transported in the bloodstream to their appropriate destinations. The outer “shell” of a lipoprotein particle is made up of a phospholipid membrane and at least one apolipoprotein.

The lipids themselves are located in the interior of the lipoprotein particle.

The apolipoproteins are a family of specialized proteins whose job is to make sure the various species of lipoproteins all do what they are supposed to do. Lipoproteins are classified according to which apolipoproteins are present on their surface.

There are five major lipoproteins:

Chylomicrons

Chylomicrons are very large lipoprotein particles that process dietary lipids. Their main apolipoprotein is called APO B-48.

After a meal, circulating chylomicrons take up ingested lipids (fatty acids and cholesterol) from the intestines into the bloodstream. The chylomicrons deliver most of their fatty acid cargo to muscles (for energy) and to the adipose tissue (for storing as fat). Whatever cholesterol and fatty acids remain in the chylomicrons are then delivered to the liver for further processing.

Chylomicrons are cleared from the circulation within a few hours after a meal. This is why dietary cholesterol contributes relatively little to our blood cholesterol levels - especially if the blood test is taken after a 12-hour fast.

VLDL, IDL, and LDL

Most of the triglycerides and cholesterol that circulate in the bloodstream are manufactured by the liver. The liver packages these lipids into Very Low Density Lipoproteins, or VLDL. (The density of a lipoprotein is largely determined by its lipid content - the more lipid, the less dense they are).

The main apolipoprotein of VLDL (and its derivatives, IDL and LDL) is apolipoprotein B-100.

As is the case with chylomicrons, VLDL releases the fatty acids it is carrying to the tissues for energy and storage. As the lipid content of VLDL diminishes, the lipoprotein becomes more dense, and eventually becomes Intermediate Density Lipoprotein, or IDL.

IDL continues releasing its lipid content to the tissues until it finally becomes Low Density Lipoprotein, or LDL. By this most of the triglycerides have been removed from the lipoprotein, leaving the LDL with a preponderance of cholesterol.

LDL particles deliver cholesterol to the tissues to maintain the integrity of cell membranes, and to make hormones. Eventually, the remnants of the LDL particles are taken back up by the liver, where the remaining cholesterol is incorporated into bile acids.

HDL

High Density Lipoproteins (HDL) remove excess cholesterol from the tissues and carry it back to the liver. Since removing excess cholesterol is thought reduce the risk of cardiovascular disease, HDL cholesterol is considered “good.” However, it’s not the cholesterol itself that is good - cholesterol is just cholesterol. What’s “good” is what the HDL lipoprotein is doing with the cholesterol. Presumably, high HDL levels mean that a lot of excess cholesterol is being removed from where it is not supposed to be.

The main apolipoprotein of HDL is APO-A.

Lipoproteins and Atherosclerosis

The development of atherosclerosis is strongly associated with excess levels of cholesterol carried by the Apo B-100-containing lipoproteins (chiefly, LDL). However, the story is more complicated than simply measuring LDL-cholesterol levels.

For instance, there are different “types” of LDL particles. Smaller, denser LDL particles are now thought to be particularly bad, because they pass more easily across blood vessel walls, where they can participate in plaque formation. Similarly, oxidized LDL is thought to be much more of a problem than non-oxidized LDL.

Furthermore, while HDL-cholesterol levels have generally been associated with a lower risk of CAD, it has become clear that there are several “species” of HDL, and that some are less “good” than others.

Bottom Line

The more scientists learn about the lipoproteins, the more complex the picture gets. Their role in maintaining the health of every tissue in the body is critical. Their role in producing - or preventing - disease is an increasingly complicated story, that is still being worked out.

Sources:

Parish S, Offer A, Clarke R, et al. Lipids and lipoproteins and risk of different vascular events in the MRC/BHF Heart Protection Study. Circulation 2012; 125:2469.

Steinberg D, Parthasarathy S, Carew TE, et al. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 1989; 320:915.

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