BINDING AND DEGRADATION OF LIPOPROTEIN(A) AND LDL BY PRIMARY CULTURESOF HUMAN HEPATOCYTES - COMPARISON WITH CULTURED HUMAN MONOCYTE-MACROPHAGES AND FIBROBLASTS

Although lipoprotein(a) (Lp[a]) has structural similarities to low-den sity lipoprotein (LDL) that include the presence of apolipoprotein B-1 00 there is some disagreement over the strength of its interaction wit h the LDL receptor and its cellular catabolism by the LDL receptor-med iated pathway. To clarify this subject we evaluated LDL receptor-media ted binding and degradation of Lp(a) and LDL in three human cell lines . The binding of 50 nmol/L Lp(a) at 37 degrees C to the LDL receptor o f primary hepatocytes, macrophages, and fibroblasts was only 10%, 29%, and 29% of the respective value obtained with 50 nmol/L LDL. Analysis of 4 degrees C binding curves indicated that Lp(a) and LDL had equal affinities for the LDL receptor of fibroblasts, whereas maximal bindin g of Lp(a) was remarkably lower than that of LDL. LDL receptor-mediate d degradation of 50 nmol/L Lp(a) in hepatocytes, macrophages, and fibr oblasts was only 17%, 22%, and 26%, respectively, of the value obtaine d with 50 nmol/L LDL and varied greatly among the cells in that it was lowest in hepatocytes, an order of magnitude greater in macrophages, and two orders of magnitude greater in fibroblasts. In contrast, the n onspecific degradation rate of Lp(a) was similar to that of LDL in eac h of the three tested cells lines. However, the proportion of the degr adation of Lp(a) that was nonspecific varied greatly, being 76%, 58%, and 33% in hepatocytes, macrophages, and fibroblasts, respectively. Th ese studies indicate that not only is Lp(a) recognized by the LDL rece ptor but also that, in fibroblasts, Lp(a) and LDL have equal affinitie s for the LDL receptor, although Lp(a) has a much lower receptor occup ancy than LDL. Additionally, they show that there are great cellular d ifferences in the LDL receptor-mediated degradation of Lp(a). If these results can be extrapolated in vivo, where normal LDL levels are 40- to 50-fold higher than those of Lp(a), it would be unlikely that the h epatic LDL receptor is significantly involved in the degradation of Lp (a).