ASSOCIATION OF LP(A) RATHER THAN INTEGRALLY-BOUND APO(A) WITH TRIGLYCERIDE-RICH LIPOPROTEINS OF HUMAN-SUBJECTS

The majority of apolipoprotein (a) [apo(a)] in plasma is characteristi cally associated with Lipoprotein (a) [Lp(a)], having a buoyant densit y (1.05-1.08 g/ml) intermediate between low density lipoproteins (LDL) and high density lipoproteins (HDL). In the fed (postprandial) state or in the presence of fasting (endogenous) hypertriglyceridemia, a sma ll proportion of plasma apo(a) is found in the density <1.006 g/ml fra ction of plasma, associated with larger and less dense triglyceride-ri ch lipoproteins (TRL). In order to further characterize the presence o f apo(a) in ultracentrifugally-separated TRL (UTC-TRL), this lipoprote in fraction was isolated from plasma obtained in the fed state (three hours after an oral fat load) from healthy normolipidemic subjects (Lp (a): 38 +/- 8 mg/dl (mean +/- S.E.), n = 4) and also from plasma obtai ned after an overnight fast from hypertriglyceridemic patients (plasma TG: 8.16 +/- 2.00 mmol/l, Lp(a): 41 +/- 3 mg/dl, n = 18). Apo(a) in 3 h-postprandial UTC-TRL (5 +/- 2% of total plasma apo(a)) and in hyper triglyceridemic UTC-TRL (8 +/- 2% total apo(a)) was separable by elect rophoresis and/or gel chromatography (FPLC) from the majority of UTC-T RL Lipid. Apo(a) in UTC-TRL fractions had slow pre-beta electrophoreti c mobility and was isolated in a lipoprotein size-range smaller than V LDL and larger than LDL, consistent with it being Lp(a). Recentrifugat ion of UTC-TRL resulted in the majority of apo(a) being recovered in t he density > 1.006 g/ml fraction. Addition of proline to plasma sample s before ultracentrifugation (final concentration: 0.1 M) substantiall y reduced the amount of Lp(a) in UTC-TRL. TRL separated from plasma by FPLC contained less apo(a) (2-5% of total plasma apo(a)), but this ap o(a) was also readily dissociable from TRL lipid, had slow pre-beta el ectrophoretic mobility, and was associated with a lipoprotein with the size of Lp(a). Our data suggest that apo(a) in the TRL fraction of su bjects with postprandial triglyceridemia or endogenous hypertriglyceri demia is not an integral component of plasma VLDL or chylomicrons, but represents the presence of non-covalently bound Lp(a).