Evidence for high density lipoproteins as the major apolipoprotein A-IV-containing fraction in normal human serum

The distribution of human apolipoprotein A-IV was studied in sera from normolipidemic fasting subjects by high performance gel filtration on a Superose 12 HR column. The major part of apolipoprotein A-IV eluted in the range of the apolipoprotein A-I peak, and distributed mainly in the large-size high density lipoprotein subfractions. Only a small peak or a shoulder on the main fraction appeared in the elution volume of free apolipoprotein A-IV. To investigate the relation of apolipoprotein A-IV with high density lipoprotein particles, serum high density lipoproteins were precipitated by incubating human serum with anti-apolipoprotein A-I immunoglobulins. At optimal concentrations, inducing a precipitation of 90 to 95% of serum apolipoprotein A-I, about 70% of serum apolipoprotein A-IV was precipitated. It was concluded that, in fasting human serum, apolipoprotein A-IV was mainly associated with high density lipoprotein particles. This high degree of association to high density lipoproteins did not result from the known in vitro redistribution of apolipoprotein A-IV induced by lecithin: cholesterol acyltransferase activity since it was observed in sera in the presence of inhibitors of this enzyme. The comparison of gel filtration profiles of total serum and of serum fractions separated by ultracentrifugation showed that the apolipoprotein A-IV-high density lipoprotein association was a weak one, easily dissociated by the ultracentrifugation process. The existence in fasting human serum of a predominant high density lipoprotein-associated form of apolipoprotein A-IV should stimulate more studies of the general function and metabolism of this protein.