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.