Insights into Lipoprotein Metabolism from Studies in Transgenic Mice

Lipoproteins are complex particles composed of various lipids and proteins that transport endogenous and dietary fats in the blood stream. There are five types of lipoprotein particles that range from smallest to largest: HDL, LDL, IDL, VLDL, and chylomicrons. Abnormal lipoprotein levels are associated with several human diseases, most commonly atherosclerosis. Individuals with atherosclerotic coronary heart disease almost invariably have one or more of four lipoprotein abnormalities: increased LDL-C; decreased HDL-C, usually associated with increased levels of triglyceride­ rich lipoproteins (VLDL); increased levels of IDL-C and chylomicron remnants; and high levels 'of an abnormal lipoprotein Lp(a) , which is a complex of LDL and a large glycoprotein called apo(a). In the last decade genes have been isolated that code for proteins that directly interact with plasma lipids, thus enabling us to better understand lipoprotein metabolism and its abnormalities. There are approximately 17 such lipoprotein transport proteins including apolipoproteins that coat lipo­ protein particles, lipoprotein processing proteins, and lipoprotein receptors (Figure 1). The genes coding for these proteins are all single copy in the human genome. They have been sequenced, mapped, and used as candidate