Human apolipoprotein A-I and A-II metabolism

Abstract

The kinetics of the major apolipoproteins (apo) of plasma high density lipoproteins (HDL), apoA-I and apoA-II, were examined in a total of 44 individual tracer studies in 22 normal male and female subjects. Following the intravenous injection of radioiodinated HDL, the specific radioactivity decay of apoA-I within HDL (residence time, 5.07 ± 1.53 days), as determined by column chromatography, was significantly (P < 0.01) faster than that of apoA-II (residence time, 5.96 ± 1.84 days). The specific radioactivity decay of apoA-I within HDL when labeled on HDL or as apoA-I was found to be almost identical. Similar results were obtained for apoA-II. Analysis of simultaneous paired radiolabeled apoA-I and apoA-II studies revealed that the mean apoA-I plasma residence time (4.46 ± 1.04 days was significantly (P < 0.01) shorter than that for apoA-II (4.97 ± 1.06 days). Females had significantly (P < 0.01) higher apoA-I plasma concentrations (124 ± 24 mg/dl) and apoA-I synthesis rates (13.58 ± 2.23 mg/kgxday) than did males (108 ± 16 mg/dl, and 11.12 ± 1.92 mg/kgxday, respectively). Plasma apoA-I levels were correlated with plasma apoA-I residence times, but not synthesis rates; and apoA-II concentrations were correlated only with apoA-II whole body residence times. ApoA-I and apoA-II plasma residence times were inversely correlated with plasma triglyceride levels. These data are consistent with the following concepts: labeling of apoA-I and apoA-II as apolipoproteins or on HDL does not affect their specific radioactivity decay within HDL; the mean residence time of apoA-I both in plasma and in HDl is significantly shorter than that of apoA-II; the increased apoA-I levels seen in female subjects are due to increased apoA-I synthesis; and the plasma apoA-I residence time, which is inversely correlated with plasma triglyceride levels, is an important determinant of apoA-I concentration in both males and females.