Receptor-mediated mechanisms of lipoprotein remnant catabolism

Chylomicron and VLDL are triglyceride-rich lipoprotein particles assembled by the intestine and liver respectively. These particles are not metabolized by the liver in their native form. However, upon entry into the plasma, their triglyceride component is rapidly hydrolyzed by lipoprotein lipase and they are converted to cholesterol-rich remnant particles. The remnant particles are recognized by the liver and rapidly cleared from the plasma. This process is believed to occur in two steps. (i) An initial sequestration of remnant particles on hepatic cell surface proteoglycans, and (ii) receptor-mediated endocytosis of remnants by hepatic parenchymal cells. The initial binding to proteoglycans may be facilitated by lipoprotein lipase and hepatic lipase which possess both lipid- and heparin-binding domains. The subsequent endocytic process may be mediated by LDL receptors and/or LRP. Both receptors have a high affinity for apoE, a major apolipoprotein component of remnant particles. The lipases may also serve as ligands for these receptors. An impairment of any component of this complex process may result in an accumulation of remnant particles in the plasma leading to atherosclerosis and coronary heart disease.