High-density lipoprotein subclasses and apolipoprotein A-I

Epidemiological and clinical studies showing an association between decreased concentrations of high-density lipoprotein (HDL) cholesterol and increased risk of premature coronary artery disease have generated interest in the mechanism through which HDL prevents atherosclerosis. Recognition of the importance of apolipoproteins (apo(s)) has led to the separation of HDL into subpopulations according to their apolipoprotein composition. It is now recognised that HDL comprises at least two types of apo A-I-containing Lipoproteins: LpA-I:A-II containing both apo A-I and apo A-II and LpA-I containing apo A-I but not apo A-II. A majority of studies support the fact that LpA-I is more effective than LpA-I:A-II in promoting cellular cholesterol efflux, the first step in reverse cholesterol transport, Studies in transgenic animals have revealed that the gene transfer of human apo A-I in mice and rabbits increases plasma apo A-I and HDL cholesterol levels and particularly apo A-I-rich HDL particle concentrations, leading to inhibition of the development of dietary or genetically induced atherosclerosis. On the other hand, gene transfer of apo A-II in mice gives conflicting results. The conclusions of some experiments indicate either an atherogenic, or a poorly anti-atherogenic, or even a strongly anti-atherogenic role for apo A-II and for apo A-II-rich HDL lipoproteins. Although these experimental results have been obtained in animals, they confirm previous studies obtained in human clinical studies, indicating that apo A-I-rich HDL (tested as LpA-I in clinical studies) are generally strong plasma markers of atherosclerosis protection while the clinical significance of apo A-If apo A-II HDL (tested as LpA-I:A-II in clinical studies) is more controversial. The introduction of immunological methods to measure LpA-I and LpA-I:A-IT levels in blood make large-scale studies feasible to confirm the clinical significance of these HDL particles. (C) 1999 Elsevier Science B.V. All rights reserved.