Lipids, mainly cholesterol and triglycerides, are transported
in human plasma by macromolecular complexes termed lipoproteins.
Lipoproteins are composed of a lipid core surrounded by apolipoproteins
that regulate the uptake and off-loading of lipids and interactions
with cell membrane receptors. The lipoproteins that are primarily
responsible for delivering cholesterol and triglycerides to peripheral
tissues originate in the liver and contain a key apoprotein called
B-100. These B-100–containing lipoproteins include very low-density lipoprotein (VLDL),low-density lipoprotein (LDL), and intermediate-density lipoprotein (IDL) (Figure
26–2). The uptake by cells of B-100–containing
lipoproteins can occur by receptor-mediated endocytosis or by scavenger
receptors. Receptor-mediated uptake is a carefully regulated process
that protects cells from being overloaded with lipids. In contrast,
uptake by scavenger receptors is an unregulated process that can
overwhelm the ability of a cell to sequester potentially toxic lipids
safely. Macrophages in arterial walls use scavenger receptors to
take up circulating lipoproteins, especially particles with apolipoproteins
that have been modified by free radicals. When these macrophages
become overloaded with lipids, they are transformed into distressed
foam cells that initiate a local inflammatory response. Engorged
foam cells, foam cells that have burst, and the products of the
inflammatory responses form the core of an atherosclerotic plaque.
Whereas plaques can slowly occlude coronary and cerebral vessels,
clinical symptoms are more frequently precipitated by rupture of
unstable plaques, leading to occlusive thrombi.