A Cellular Basis for the Potential Atherogenicity of Triglyceride-Rich Lipoproteins

Abstract

Two potential intiating events in atherosclerosis are endothelial injury and the accumulation of lipid-filled foam cells in the arterial intima. Ross and Glomset suggested that atherosclerosis may be a response to some form of endothelial injury (1). By this mechanism, changes in endothelial permeability could expose the arterial intima, the site of plaque initiation, to all blood components, including monocytes, lipoproteins, platelets, and coagulation factors with ensuing lipid accumulation and fibrin deposition. A second important initiating event in atherosclerosis is the accumulation of foam cells in the intima of the arterial wall (2–4). Many arterial foam cells are monocyte-derived macrophages that are engorged with cholesteryl ester (5). LDL are the major carriers of cholesterol in the blood and have long been considered to be the primary atherogenic lipoprotein. This represents a paradox in terms of the initiation of atherosclerosis, however, since native, unmodified LDL are not toxic in endothelial cells and do not produce foam cells in vitro when incubated with macrophages.