Postprandial changes in apolipoprotein(a) concentration of triglyceride-rich lipoproteins can be reproduced by in vitro incubation: implications for underlying mechanism

We investigated the reciprocal changes in apolipoprotein(a) concentration in the lipoprotein of d > 1.006 and the triglyceride-rich lipoprotein (TRL) fractions of plasma which occur in vivo following fat ingestion. Twenty fasting subjects were studied before and 4 h after a fat-rich meal. In 75% of cases, in vitro incubation of the postprandial (4-h) TRL with autologous fasting (0-h) lipoproteins of d > 1.006 resulted in further substantial (>5% total) reciprocal changes in apo(a) concentration of the 2 fractions. The increase in re-isolated postprandial TRL apo(a) was 25.1% ± 5.1% of the total apo(a), compared to the insignificant increase (0.1% ± 0.1%) in re-isolated fasting TRL. Most of the further increase in 4-h TRL apo(a) (94% ± 4%) could be achieved by incubation with the corresponding 4-h chylomicron fraction (CM) alone. The re-isolated 4-h TRL apo(a) concentration correlated positively with 4-h plasma TG concentration (r = 0.65, P < 0.01) and other indices of postprandial lipaemia. In vitro incubation of pooled serum lipoproteins of d > 1.006 with serial dilutions of nascent CM obtained from chylous ascitic fluid revealed that the reciprocal changes in apo(a) concentration exhibit a curvilinear relationship with the concentration of CM triglyceride which plateaued round 7 mmol/1 in this instance. We conclude that the reciprocal changes in apo(a) concentration between TRL and lipoproteins of d > 1.006 which occur in the postprandial phase are quantitatively significant and largely represent a redistribution process rather than de novo synthesis because they can be reproduced by in vitro incubation.