Atherosclerosis and apoprotein E. An enigmatic relationship

In this article, we consider the role of apoprotein E in lipoprotein metabolism and especially in the metabolism of potentially atherogenic lipoproteins. Particular consideration has been given to three features of apoprotein E involvement in lipid cell interactions. Evidence implicating free cholesterol as a mediator of apoprotein E biosynthesis in cholesterol-loaded macrophages is presented. Experiments pointing to apoprotein E as the ligand promoting the interaction of beta-very-low-density lipoprotein (beta-VLDL) with macrophages are summarized. Finally, we describe the influence of fat and cholesterol fed to rhesus monkeys and baboons on the generation of hepatogenous (from isolated liver perfusates) VLDL enriched in cholesterol ester and apoprotein E. These hepatic VLDLs, none of which exhibits beta-electrophoretic mobility, promote cholesterol esterification in macrophages in proportion to their apoprotein E content. The complex role of apoprotein E in the genesis and reversal of atherosclerosis is briefly discussed.