| Abstrakt: |
The metabolism of apolipoproteins A-I and A-II, as well as other high density lipoprotein (HDL) constituents, was studied in patients with homozygous familial HDL deficiency (Tangier disease) prior to and after plasma exchange or HDL infusion. Mean plasma apoA-I, apoA-II, and HDL cholesterol values in homozygotes (n = 2) were 2.0 mg/dl, 2.7 mg/dl, and 1.5 mg/dl, respectively, and in a normal control subject were 125.1 mg/dl, 23.0 mg/dl, and 53.0 mg/dl, respectively. Based on radioiodinated apoA-I and apoA-II kinetic studies in the baseline state, synthesis rates for apoA-I and apoA-II in mg/kg/day were 3.81 and 1.61, respectively, in one homozygote (patient B) and 11.82 and 1.99, respectively, in the normal subject. ApoA-I and apoA-II plasma residence times in days were 0.22 and 0.81, respectively, in the homozygote, and 4.04 and 4.44, respectively, in the normal subject. These data indicate that this homozygote had both a moderate decrease in the synthetic rates of apoA-I and apoA-II, as well as a marked decrease in the plasma residence times of these two apolipoproteins. In one homozygote (patient A) following a complete plasma exchange during cardiopulmonary bypass, plasma HDL cholesterol, apoA-I, and apoA-II levels were very similar to pre-exchange values within 64 hr after exchange. A second homozygote (patient B) received HDL intravenously as well as 125I-labeled apoA-I and 131I-labeled apoA-II. Following infusion, the residence time in days for HDL subfractions, HDL2b, HDL2a, and HDL3 were 0.1, 0.8, and 2.7, respectively. HDL protein and phospholipid both had a monoexponential decay, with residence times of 0.7 days, while HDL triglyceride disappeared monoexponentially with a residence time of 0.5 days. HDL cholesterol had a biexponential decay, with the residence time of the slow component being 0.7 days. Plasma and HDL apoA-I decayed down to baseline values significantly faster than did plasma and HDL apoA-II. ApoA-II specific radioactivity decreased throughout the course of the infusion study in both plasma and HDL, while apoA-I specific radioactivity decreased slightly, then rose, and subsequently declined in both plasma and HDL. The data indicate that the rapid and altered catabolism of apoA-I and apoA-II in Tangier homozygotes persists despite major increases in the plasma pool size of these proteins. In addition, following HDL infusion, HDL2b and HDL2a disappeared at a faster rate than HDL3, HDL cholesterol and triglyceride were catabolized at a faster rate than HDL protein and phospholipid, and apoA-I disappeared more rapidly than apoA-II. These observations may have important implications with regard to the catabolism of HDL subfractions and constituents in normal man. |
