Mark R. McCall

The role of apolipoprotein A-l-containing lipoproteins in atherosclerosis

The inverse relationship between HDL and apolipoprotein A-l concentrations and the risk for premature atherosclerosis is well established, but the mechanism whereby apolipoprotein A-l offers protection is still somewhat elusive. Recent studies suggest that a specific subpopulation within the lipoprotein (Al) subclass may be more effective than others in promoting cholesterol efflux from cells. In addition, it appears that the lipid-free form of apolipoprotein A-l may have an important role in the antiatherosclerotic process. Unique new functions of apolipoprotein A-l-containing particles in modulating cytokines and lipid hydroperoxide transport, together with their role in antiatherogenesis, are also discussed. Current research with transgenic mice, however, indicates that apolipoprotein A-ll must be taken into consideration in understanding the development of atherosclerosis, because it appears to be a potent antagonist for the protective properties of apolipoprotein A-l.

Dissociable and nondissociable forms of platelet-activating factor acetylhydrolase in human plasma LDL: implications for LDL oxidative susceptibility

Platelet-activating factor acetylhydrolase (PAF-AH) is transported by lipoproteins in plasma and is thought to possess both anti-inflammatory and anti-oxidative activity. It has been reported that PAF-AH is recovered primarily in small, dense LDL and HDL following ultracentrifugal separation of lipoproteins. In the present studies, we aimed to further define the distribution of PAF-AH among lipoprotein fractions and subfractions, and to determine whether these distributions are affected by the lipoprotein isolation strategy (FPLC versus sequential ultracentrifugation) and LDL particle distribution profile. When lipoproteins were isolated by FPLC, the bulk (approximately 85%) of plasma PAF-AH activity was recovered within LDL-containing fractions, whereas with ultracentrifugation, there was a redistribution to HDL (which contained approximately 18% of the activity) and the d>1.21 g/ml fraction (which contained approximately 32%). Notably, re-ultracentrifugation of isolated LDL did not result in any further movement of PAF-AH to higher densities, suggesting the presence of dissociable and nondissociable forms of the enzyme on LDL. Differences were noted in the distribution of PAF-AH activity among LDL subfractions from subjects exhibiting the pattern A (primarily large, buoyant LDL) versus pattern B (primarily small, dense LDL) phenotype. In the latter group, there was a relative depletion of PAF-AH activity in subfractions in the intermediate to dense range (d=1.039-1.047 g/ml) with a corresponding increase in enzyme activity recovered within the d>1.21 g/ml ultracentrifugal fraction. Thus, there appears to be a greater proportion of the dissociable form of PAF-AH in pattern B subjects. In both populations, most of the nondissociable activity was recovered in a minor small, dense LDL subfraction. Based on conjugated dienes as a measure of lipid peroxidation, variations in PAF-AH activity appeared to contribute to variations in oxidative behavior among ultracentrifugally isolated LDL subfractions. The physiologic relevance of PAF-AH dissociability and the minor PAF-AH-enriched oxidation-resistant LDL subpopulation remains to be determined.