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.
Trieu
V N
VN
Lipoprotein and Atherosclerosis Research Program, Oklahoma Medical Research Foundation, Oklahoma City 73104.
McConathy
W J
WJ
D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism*; D002417:Cattle; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006801:Humans; D007700:Kinetics; D017270:Lipoprotein(a); D008074:Lipoproteins / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism
D001055:Apolipoproteins B; D017270:Lipoprotein(a); D008074:Lipoproteins; D008077:Lipoproteins, LDL; D010958:Plasminogen