LDL cholesterol

Low density lipoproteins (LDLs) are lipid storage molecules formed by the action of extrahepatic lipoprotein lipase on VLDL and intermediate density lipoprotein molecules. They have a half-life of days. About two-thirds to four-fifths of serum cholesterol is present in LDL.

LDL has relatively sparse triglyceride stores at only 6-8% of its mass. However, it is relatively rich in cholesterol and cholesterol esters at nearly 50% of its mass - it forms the main particle conveying cholesterol from the liver to extrahepatic tissue. Extrahepatic cells recognize LDL by the apoprotein B-100 on its surface. LDL is taken up by receptor-mediated endocytosis. The receptor is termed the LDL receptor and mutations of it lead to familial hypercholesterolaemia.

During transit, LDL interacts with HDL to obtain protein in order to increase stability. In return, LDL passes cholesterol esters to HDL.

Note that the heterogeneity in LDL particle composition, as a result of differences in the amount of cholesterol per LDL particle, means that measurement of LDL cholesterol is not equivalent to measurement of LDL-particles. This is significant because:

• increased concentrations of small, dense, cholesterol-depleted particles are often observed in patients with vascular disease; also cholesterol-depleted LDL levels are often raised in patients with hypertriglyceridaemia even when serum cholesterol is low
• the cholesterol-depleted LDL particles are more atherogenic than cholesterol-rich LDL particles - also they are not readily removed via the LDL receptors
• small, dense LDL (and thus a relative increased level of apo B than would be anticipated from serum cholesterol or LDL values) occur because cholesteryl ester and triglycerides can exchange between lipoproteins, whereas apo B present in LDL and VLDL cannot (transfer of cholesteryl ester is mediated via cholesteryl transfer protein (CETP)). CETP facilitates the transfer of cholesteryl ester from HDL and LDL to VLDL - this transfer is increased if VLDL levels are high (which generally occurs in hypertriglyceridaemia). This process leads to a reduction in HDL cholesterol and formation of cholesterol-depleted LDL (there is also transfer of triglyceride from VLDL into HDL and LDL). As the LDL passes through the liver the triglyceride is removed - this then leads to the formation of small, dense LDL

A low HDL cholesterol is a clue to the presence of cholesterol-depleted (small, dense) LDL.