IN-VIVO KINETICS OF LIPOPROTEIN(A) IN HOMOZYGOUS WATANABE HERITABLE HYPERLIPEMIC RABBITS

In vivo kinetics of lipoprotein(a) [Lp(a)] were investigated in homozygous Watanabe heritable hyperlipidaemic (WHHL) rabbits (an animal model of familial hypercholesterolemia (FH)), and in normolipidemic Japanese White rabbits (controls). I-125-labelled Lp(a) and I-131-labelled LDL were simultaneously injected intravenously. Blood samples were then taken periodically. Kinetic parameters were calculated from the plasma radioactivity decay curves. The fractional catabolic rates (FCRs) of both Lp(a) and LDL (1.355+/-0.189 pools per day and 1.278+/-0.397 pools per day, respectively) in the WHHL rabbits were significantly (P<0.005) smaller than those in the control rabbits (2.008+/-0.083 pools per day and 2.855 +/- 0.759 pools per day, respectively). In WHHL rabbits, the FCRs of Lp(a) and LDL were similar. However, in control rabbits, the FCR of Lp(a) was significantly (P<0.01) smaller than that of LDL. In WHHL rabbit organs, the mean ratio I-125-Lp(a): I-131-LDL, 48 h after injection, normalized to the corresponding isotope ratio in plasma, were 1.525, 1.020, 1.819 and 1.967, in liver, kidney, spleen and bile, respectively. These values were significantly higher than the corresponding values in control rabbits (0.590, 0.677, 0-862 and 0.766, respectively). Our data strongly suggest that Lp(a) clearance is not entirely dependent upon LDL receptors and may be mediated by some other mechanisms.