CELL-SURFACE ASSEMBLY OF LIPOPROTEIN(A) IN PRIMARY CULTURES OF BABOONHEPATOCYTES

Lipoprotein(a) (Lp(a)) consists of a low density lipoprotein particle in which apolipoprotein(a) (apo(a)), is disulfide linked to apoB. Lp(a ) is produced by the liver, and high plasma levels represent an indepe ndent risk factor for cardiovascular diseases. However, pathways of pr oduction and metabolism of Lp(a) are poorly understood. We used primar y cultures of baboon hepatocytes to analyze the steps involved in Lp(a ) biogenesis. The results demonstrated that Lp(a) assembly was extrace llular, since it was inhibited when anti apo(a) antiserum was present in the culture medium. In addition, free apo(a) produced by hepatocyte s could associate extracellularly with apoB in either very low density or low density Lipoproteins. Lp(a) assembly required lysine-binding p ockets in apo(a) kringles, as it was inhibited by the lysine analog, 6 -amino hexanoic acid. A portion of apo(a) was also bound to the cell s urface via its kringle domains and could be released into the medium b y 6-amino hexanoic acid or proline. In add-back experiments, apo(a), b ut not Lp(a), bound to the cell surface. Addition of low density lipop rotein or very low density Lipoprotein to hepatocyte cultures released apo(a) from the cell surface into the lipoprotein fraction of culture medium. We conclude that assembly of Lp(a) can occur at the cell surf ace. This represents one potential mechanism of Lp(a) production in vi vo.