Lipoproteins containing apolipoprotein A-I extracted from human aortas

Apolipoprotein A-I was quantitated by electroimmunoassay in buffer-soluble fractions of both grossly normal intima and raised atherosclerosis lesions of the human aorta. The mean value for apolipoprotein A-I content in microgram/mg tissue dry weight of normal intima (12 cases) was 0.71 +/- 0.10 S.E. and of aortic plaques (19 cases) was 0.64 +/- 0.40 S.E. When compared to the buffer-extractable apolipoprotein B content measured in these same cases from both regions, the ratio of apolipoprotein B to apolipoprotein A-I was approximately 6. No apolipoprotein A-I was measurable in tunica media. Following differential ultracentrifugation into d less than 1.063, d 1.063-1.21 and d greater than 1.21 fractions, the distributions of recovered apolipoprotein A-I were, respectively: 1, 94 and 5% for normal intima, 19, 31 and 50% for plaques and 1, 89 and 10% for plasma. Characterization of a chromatographically purified d 1.063-1.21 or HDL density fraction from fatty-fibrous plaques demonstrated particles of between 60 and 120 A diameter, a characteristic apolipoprotein A-I band by SDS-polyacrylamide gel electrophoresis, and a precipitin peak closely migrating with that for plasma HDL by two-dimensional immunoelectrophoresis. The d greater than 1.21 density fraction from plaques isolated by affinity chromatography on a Sepharose-anti-apolipoprotein A-I column contained small amounts of phospholipid but no measurable cholesterol. The d 1.063-1.21 density fraction from plaques showed a significant increase in percent free cholesterol and phospholipid contents and decrease in cholesteryl ester content relative to plasma HDL. This increase in free cholesterol could represent evidence for an anti-atherogenic mechanism wherein infiltrated HDL removes cholesterol together with phospholipid from the arterial wall.