Lipoprotein(a) binding to other apolipoprotein B containing lipoproteins.

A method combining ligand dot blotting and digital imaging was used to determine the apparent dissociation constant (KD) for the binding of lipoprotein(a) to low-density lipoproteins (Lp(a)-LDL2). By use of this approach, the KD for the Lp(a)-LDL2 complex was shown to be in the nanomolar range [(1.05 +/- 0.21) x 10(-8) M, n = 4]. The Lp(a)-LDL2 interaction was both hydrophobic and ionic; however, hydrophobic forces predominated because the interaction was demonstrable at high salt concentration (greater than 2 M NaCl), while no complex was detectable at low salt concentration (less than 0.08 M NaCl). Consistent with the hydrophobic nature of this interaction, the Lp(a)-LDL2 complex was stable over a wide pH range (4-10). Plasminogen did not compete with Lp(a) binding to LDL2 even at a 2.2 X 10(3) molar excess of plasminogen over the LDL2 concentration. The only component identified in plasma and serum that inhibited the binding of LDL2 to Lp(a) was apolipoprotein B containing lipoproteins (apoB-Lp). These studies indicate that the Lp(a)-LDL2 complex could exist in plasma. In fact, up to 72% of purified Lp(a) added to an Lp(a)-negative hypertriglyceridemic plasma floated with apoB-Lp (d less than 1.063 g/mL) following ultracentrifugation, whereas only 9% of the purified Lp(a) added to the apoB-Lp-free 1.12 g/mL infranate floated at d less than 1.063 g/mL. The formation of a complex of Lp(a) with apoB-Lp could increase the amount of cholesterol ester bound per cellular receptor, e.g., LDL receptor, and thus potentially accelerate cholesterol removal from the vascular compartment.