LIPOPROTEIN METABOLISM AND ATHEROSCLEROSIS
The major lipids of plasma, cholesterol and triglyceride, are transported in molecular complexes called lipoproteins. The basic structure of all lipoproteins is similar. They contain a core of neutral lipid (triglyceride and cholesterol ester) that is surrounded by a polar coat containing nonesterified cholesterol, phospholipid, and proteins (called apolipoproteins) (Fig. 29–1). The major categories of lipoproteins consist of low-density lipoprotein (LDL), very-low-density lipoprotein Davidson MH, Hirsh BJ, et al: Genetics and causality of triglyceride-rich lipoproteins inatherosclerotic cardiovascular disease. J Am Coll Cardiol. 2014 Dec 16;(VLDL), high-density lipoprotein (HDL), and chylomicrons. These lipoproteins vary in size and density (Fig. 29–2). Because lipoproteins can be separated by electrophoresis, they also have been named according to their migration relative to serum proteins. LDL is called beta lipoprotein, VLDL is pre-beta lipoprotein, and HDL is alpha lipoprotein.
Lipoprotein structure. Because cholesterol and triglycerides are hydrophobic lipids that are insoluble in plasma, intravascular transport cannot occur with these lipids in their free state. Consequently, cholesterol esters and triglycerides are packaged into spherical lipoprotein particles that span a wide range of particle size and density. Lipoprotein particles are configured so that the outer surface is polar and the inner core is nonpolar. The surface of lipoprotein particles is composed of a phospholipid monolayer, nonesterified cholesterol, and various apolipoproteins. The core of lipoprotein particles contains variable amounts of cholesterol ester and triglycerides. Reproduced with permission from Davidson MH, Toth PP, Maki KC:Therapeutic Lipidology. Totowa: Humana Press; 2007.
Spectrum of lipoprotein particles. Cholesterol and triglycerides are lipid measures used to infer the amount of various lipoprotein particles. HDL, high-density lipoprotein, IDL, intermediate-density lipoprotein; LDL, low-density lipoprotein, Lp(a), lipoprotein a, VLDL, very-low-density lipoprotein.
The primary function of lipoproteins is to transport triglycerides and cholesterol. 1,2,3,4,5 The major forms of triglyceride-rich lipoproteins (TGRLs) are chylomicrons (Fig. 29–3) 6,7 and VLDLs (Fig. 29–4). Chylomicrons are synthesized in the liver from dietary fat. They are secreted into the circulation for transport of lipids to tissues. In the circulation, chylomicron triglyceride undergoes hydrolysis by an enzyme, lipoprotein lipase (LPL), located on the surface of capillary endothelial cells; fatty acids released during lipolysis are taken up by adipose tissue and muscle. In addition, the liver synthesizes triglyceride from fatty acids and incorporates it into VLDL particles. VLDL triglyceride likewise undergoes lipolysis, releasing fatty acids for adipose tissue and muscle. Following triglyceride lipolysis, an intermediate lipoprotein, called a VLDL remnant, is formed. A portion of VLDL remnants is removed by the low-density lipoprotein receptor (LDLR), but most VLDL is converted through intermediate lipoproteins to LDL. The latter is removed from the circulation by LDLRs that are located ...