GENETIC BUT NOT DIET-INDUCED HYPERCHOLESTEROLEMIA CAUSES LOW APOLIPOPROTEIN A-IV LEVEL IN RABBIT SERA

The present report describes a competitive enzyme immunoassay for rabb it apolipoprotein A-IV (ape A-IV). This assay was applied to the deter mination of its concentration and distribution in sera from normolipid emic and hyperlipidemic rabbits. The assay was sufficiently sensitive to study this 42-kDa protein in lipoproteins fractionated from 200 mu l 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 cholestero l (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 reduc ed level of apo A-IV (3.8 +/- 1.14 mg/dl, n = 7). In each of the group s studied, apo A-IV was distributed in two distinct pools; a high-dens ity lipoprotein(HDL) associated pool and a lipoprotein-free pool. Howe ver, compared to normal, the distribution of apo A-IV in WHHL rabbit s era was shifted towards the lipoprotein-free pool. Consistent with pre viously reported observations on apo A-I, these results are compatible with the hypothesis of an impaired reverse transport of cholesterol i n WHHL rabbits, an animal model for familial hypercholesterolemia.