APOA-II KINETICS IN HUMANS USING ENDOGENOUS LABELING WITH STABLE ISOTOPES - SLOWER TURNOVER OF APOA-II COMPARED WITH THE EXOGENOUS RADIOTRACER METHOD

ApoA-II is a major apolipoprotein constituent of high density lipoprot eins (HDL) and may play an important role in lipoprotein metabolism an d predisposition to atherosclerosis. Previous radiotracer kinetic stud ies have suggested thar the metabolism of apoA-II in humans may be dif ferent than the metabolism of apoA-I, the major HDL apolipoprotein. In the present study, we have used an endogenous labeling technique usin g stable isotopically labeled amino acids to study apoA-II metabolism and compared the results to those obtained by a simultaneous exogenous radiotracer labeling method. Seven subjects with HDL cholesterol leve ls ranging from 9 to 93 mg/dl and apoA-II levels from 13 to 60 mg/dl w ere investigated in this study. [C-13(6)]phenylalanine and I-131-label ed apoA-II were simultaneously administered as a primed-constant infus ion and a bolus injection, respectively. In the endogenous labeling st udy, plateau tracer/tracee ratios of VLDL apoB-100 were used as estima tes for the precursor pool tracer/tracee ratios for apoA-II synthesis. Residence times of apoA-II using these two independent methods were f ound to be highly correlated (r = 0.973, P < 0.0002). These results in dicate that the endogenous labeling of apoA-II using stable isotopical ly labeled amino acids is a reasonable alternative to the conventional exogenous radiotracer labeling method for the investigation of apoA-I I turnover. However, under the conditions of our experimental design a nd modeling strategy, the apoA-II residence times as determined by end ogenous labeling were significantly longer (mean 5.33 days) than by ex ogenous radiotracer (mean 4.65 days). This suggests that apoA-II turno ver may be even slower than believed based on radiotracer studies, and further supports the concept that HDL containing apoA-II are metaboli zed differently than HDL without apoA-II.