The present report describes a competitive
enzyme immunoassay for rabbit
apolipoprotein A-IV (
apo A-IV). This assay was applied to the determination of its concentration and distribution in sera from normolipidemic and hyperlipidemic rabbits. The assay was sufficiently sensitive to study this 42-kDa
protein in
lipoproteins fractionated from 200 microliters of serum by FPLC gel filtration. In normolipidemic sera (n = 8),
apo A-IV concentration was 5.32 +/- 0.76 mg/dl. A diet rich in
cholesterol (0.5%), which induced an 18-fold increase in serum
cholesterol, did not significantly alter
apo A-IV concentration (6.65 +/- 1.52 mg/dl, n = 8). By contrast, genetically induced
hypercholesterolemia (Watanabe heritable
hyperlipidemia, WHHL mutation) caused a significantly reduced level of
apo A-IV (3.8 +/- 1.14 mg/dl, n = 7). In each of the groups studied,
apo A-IV was distributed in two distinct pools; a
high-density lipoprotein-(HDL) associated pool and a
lipoprotein-free pool. However, compared to normal, the distribution of
apo A-IV in WHHL rabbit sera was shifted towards the
lipoprotein-free pool. Consistent with previously reported observations on
apo A-I, these results are compatible with the hypothesis of an impaired reverse transport of
cholesterol in WHHL rabbits, an animal model for
familial hypercholesterolemia.