The formation of LDL: mechanisms and regulation

Low density lipoproteins (LDL) in blood plasma and their immediate precursors are generally thought to be the major atherogenic lipoproteins. The initial indications that LDL are formed from very low density lipoproteins (VLDL) were obtained more than 25 years ago (1, 2), yet even today the precise mechanism of LDL formation from VLDL is unknown. During the last 15 years the processes of interconversion of lipoproteins and their component lipids and proteins have been studied intensively (3). Essentially all of the approaches used in these investigations, ranging from in vitro studies of lipolysis products to multicompartmental kinetic analysis of tracers injected into humans, have been applied to study the formation of LDL. The complexity of VLDL metabolism has become particularly evident during the last 5 years and some of the truisms concerning LDL formation have had to be reconsidered. In this brief review, I describe those aspects of VLDL metabolism that are central to the mechanism of LDL formation. Recently discovered factors that influence the extent to which VLDL particles are converted to LDL and the question of VLDL-independent LDL formation will then be considered. Finally, some contemporary approaches to these issues will be addressed.