How LDL Cholesterol Becomes Atherosclerotic Plaque

Here’s an interesting article about how high levels of LDL cholesterol end up causing atherosclerosis.

The body uses cholesterol for various purposes, and it has a system for transporting cholesterol in the bloodstream. Like fat, cholesterol doesn’t dissolve in water. To transport fat and cholesterol via the bloodstream, the body puts them in packages called lipoproteins. As the name suggests, a lipoprotein contains fatty substances (lipids) as well as some protein.

Not only do fatty substances like cholesterol fail to dissolve in water, they float on top of it. That’s because they are less dense than water. They are also less dense than protein. The lipoprotein particles that are largest and contain the most fat also have the lowest density. The “bad” cholesterol that people talk about is low-density lipoprotein (LDL). These are lipoprotein particles that carry fat and cholesterol from the liver to the rest of the body. LDL is like a wheelbarrow full of fat and cholesterol traveling from the liver to the rest of the body. In contrast, high-density lipoprotein (HDL) picks up the cholesterol from the tissues and carries it back to the liver. HDL is like a mostly empty wheelbarrow picking up fat and cholesterol and taking it back to the liver.

The article explains that cholesterol is always entering and leaving the intimal layer of the arterial wall. The cholesterol is brought in by LDL and is taken away by HDL. If the cholesterol is brought in faster than it leaves, it builds up to form a deposit called an atheroma. The more LDL there is in the bloodstream, the faster the LDL particles enter the wall of the arteries. The cholesterol is likely to build up into an atheroma if there isn’t enough HDL to carry the cholesterol back out fast enough or if the LDL undergoes some chemical change within the wall of the artery before it can be removed. Here’s an article that explains the kinds of chemical changes that can occur to the LDL while its inside the arterial wall.

Why does cholesterol build up in the intima of the arterial wall but not in other kinds of tissue? It’s because the concentration of LDL is far higher in the arterial intima than in any other tissue. The probable reason for this high LDL concentration is the fact that the arterial intima is not drained by lymph vessels. LDL particles are small enough to leak through the gaps between the endothelial cells that pave the inner surface of the artery. Then, they can diffuse throughout the loose structure of the arterial intima. However, they are too big to leak through the pores in the carbohydrate-and-protein meshwork of the medial layer. Thus, they cannot make their way through to the lymphatic system, which is highly efficient at carrying lipoproteins back to the bloodstream.
Photo by Oregon State University