PRODUCTION-RATE DETERMINES PLASMA-CONCENTRATION OF LARGE HIGH-DENSITY-LIPOPROTEIN IN NONHUMAN-PRIMATES

Large LpAI HDL particles, containing only apoA- I without apoA-II, are reported to be the major anti-atherogenic portion of HDL and to be in creased in individuals with low risk for coronary heart disease. To de termine whether the plasma concentration of large LpAI is modulated by the rate of production or catabolism of apolipoprotein A-I (apoA-I) i n large LpAI, kinetic studies of large LpAI were performed in African green monkeys consuming an atherogenic diet with either high plasma HD L concentration (120 +/- 36 mg/dl, mean +/- SD, n = 3) or lo tv plasma I-IDL concentration (40 +/- 13 mg/dl, n = 3), Large LpAI was isolated , without ultracentrifugation, by immunoaffinity and gel filtration an d radiolabeled, After injection, the specific activity of apoA-I in la rge HDL, consisting of both LpAI and LpAI:AII particles, was followed, A multicompartmental model was developed for the kinetics of apoA-I i n large HDL, which indicated that a portion of large HDL is distribute d to a sequestered pool, outside the circulating plasma, and reenters circulating plasma approximately 3 h after injection, There was no con version of large LpAI to smaller HDL particles or transfer of radiolab eled apoA-I to smaller HDL particles. Although the mean fractional cat abolic rate was not different comparing the high and low HDL group, th e mean production rate of apoA-I in large HDL tvas l-fold greater in t he high HDL group compared with the low HDL group. These data support the hypothesis that the plasma concentration of large HDL is controlle d primarily by the rate of production of apoA-I in large HDL.