Genetic but not diet-induced hypercholesterolemia causes low apolipoprotein A-IV level in rabbit sera.
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.
Mezdour
H
H
Department of Etiology and Pathophysiology, National Cardiovascular Center Research Institute, Osaka, Japan.
Yamamura
T
T
Nomura
S
S
Yamamoto
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001054:Apolipoproteins A / Q000097:blood* / Q000235:genetics / Q000302:isolation & purification; D002850:Chromatography, Gel; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D006937:Hypercholesterolemia / Q000097:blood / Q000235:genetics*; D007106:Immune Sera; D007124:Immunoenzyme Techniques; D008969:Molecular Sequence Data; D009154:Mutation; D011817:Rabbits; D013045:Species Specificity
D001054:Apolipoproteins A; D007106:Immune Sera; C022205:apolipoprotein A-IV