Low-density lipoprotein (LDL) belongs to the lipoprotein particle family. Its size is approx. 22 nm and its mass is about 3 million daltons; but, since LDL particles contain a changing number of fatty acids, they actually have a mass and size distribution. Each native LDL particle contains a single apolipoprotein B-100 molecule (Apo B-100, a protein with 4536 amino acid residues) that circles the fatty acids, keeping them soluble in the aqueous environment. In additon, LDL has a highly-hydrophobic core consisting of polyunsaturated fatty acid known as linoleate and about 1500 esterified cholestrol molecules. This core is surrounded by a shell of phospholipids and unesterified cholestrol as well as a single copy of B-100 large protein (514 kD).
Because LDLs transport cholesterol to the arteries and can be retained there by arterial proteoglycans starting the formation of plaques, increased levels are associated with atherosclerosis, and thus heart attack, stroke, and peripheral vascular disease. For this reason, cholesterol inside LDL lipoproteins is often called "bad" cholesterol. This is a misnomer. The cholesterol transported on LDL is the same as cholesterol transported on other lipoprotein particles. The cholesterol itself is not "bad"; rather, it is how and where the cholesterol is being transported, and in what amounts over time, that causes adverse effects.
Increasing evidence has revealed that the concentration and size of the LDL particles more powerfully relates to the degree of atherosclerosis progression than the concentration of cholesterol contained within all the LDL particles. The healthiest pattern, though relatively rare, is to have small numbers of large LDL particles and no small particles. Having small LDL particles, though common, is an unhealthy pattern; high concentrations of small LDL particles (even though potentially carrying the same total cholesterol content as a low concentration of large particles) correlates with much faster growth of atheroma, progression of atherosclerosis and earlier and more severe cardiovascular disease events and death.
LDL is formed as VLDL lipoproteins lose triglyceride through the action of lipoprotein lipase (LPL) and become smaller and denser, containing a higher proportion of cholesterol.
A hereditary form of high LDL is familial hypercholesterolemia (FH). Increased LDL is termed hyperlipoproteinemia type II (after the dated Fredrickson classification).
LDL poses a risk for cardiovascular disease when it invades the endothelium and becomes oxidized, since the oxidized form is more easily retained by the proteoglycans. A complex set of biochemical reactions regulates the oxidation of LDL, chiefly stimulated by presence of free-radicals in the endothelium. Nitric oxide down-regulates this oxidation process catalyzed by L-arginine. In a corresponding manner, when there are high levels of asymmetric dimethylarginine in the endothelium, production of nitric oxide is inhibited and more LDL oxidation occurs.