Atheroprotective mechanisms of HDL

The aim of this review was to bring together results obtained from studies on different aspects of HDL as related to CHD and atherosclerosis. As ather osclerosis is a multistep process, the various components of HDL can interv ene at different stages, such as induction of monocyte adhesion molecules, prevention of LDL modification and removal of excess cholesterol by reverse cholesterol transport. Transgenic technology has provided a model for athe rosclerosis, and permitted evaluation of the contributions of different HDL components towards the global effect. The availability of apo AIV transgen ic mice amplified the results obtained from apo AI overexpressors with resp ect to prevention of atherosclerosis. Prevention of atherosclerosis in apo E deficient mice by relatively small amounts of macrophage derived apo E ma y open new possibilities for therapeutic intervention. Contrary to early no tions, increased plasma levels of CETP, even in the presence of low but fun ctionally normal HDL, were atheroprotective. The extent to which paraoxonas e and apo J participate in prevention of human atherosclerosis needs furthe r evaluation. The findings that LCAT overexpression in rabbits was atheropr otective in contrast to increase in atherosclerosis in h LCAT tg mice, whic h was only partially corrected by CETP expression, call for some caution in the extrapolation of results from transgenic animals to humans. The import ant discovery of SR-BI as the receptor for selective uptake of CE from HDL revived interest in the clearance of CE from plasma. This pathway supplies also the vital precursor for steroidogenesis in adrenals and gonads and was shown to be dependent on apo AI. (C) 1999 Elsevier Science Ireland Ltd. Al l rights reserved.