Isolation, quantitation, and characterization of a stable complex formed by Lp[a] binding to triglyceride-rich lipoproteins.
Lipoprotein [a] (Lp[a]) is a cholesterol-rich lipoprotein resembling LDL to which a large polymorphic glycoprotein, apolipoprotein [a] (apo[a]), is covalently coupled. Lp[a] usually exists as a free-standing particle in normolipidemic subjects; however, it can associate noncovalently with triglyceride-rich lipoproteins in hypertriglyceridemic (HTG) subjects. In this study, 10-78% of the Lp[a] present in five HTG subjects was found in the triglyceride-rich lipoprotein (TRL) fraction. The Lp[a]-TRL complex was resistant to dissociation by ultracentrifugation (UCF) alone, but was quantitatively dissociated by UCF in the presence of 100 mM proline. Of this dissociated Lp[a], 70-88% was in the form of a lipoprotein resembling conventional Lp[a]. Incubation of Lp[a]-depleted TRL with native Lp[a] resulted in a reconstituted Lp[a]-TRL complex that closely resembled the native isolates in all examined properties. Complex formation was inhibited by several compounds in the order proline > tranexamate > epsilon-aminocaproate >> arginine > lysine. Neither plasminogen nor LDL inhibited binding of Lp[a] to TRL. We observed the preferential binding of Lp[a] containing higher apparent molecular weight apo[a] polymorphs to TRL both in native and reconstituted Lp[a]-TRL complexes. A disproportionate amount of Lp[a] was bound to the larger TRL particles. Although most apo[a] bound to TRL was in the form of conventional Lp[a] particles, lipid-free recombinant apo[a] was observed to bind TRL. These results provide unequivocal evidence of the existence of an Lp[a]-TRL complex under pathophysiologic conditions. The metabolic fate of the Lp[a]-TRL complex, which is more abundant in hypertriglyceridemia, may be different from that of conventional Lp[a], and may contribute uniquely to the progression or severity of cardiovascular disease.
Gaubatz
J W
JW
Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Hoogeveen
R C
RC
Hoffman
A S
AS
Ghazzaly
K G
KG
Pownall
H J
HJ
Guevara
J
J
Koschinsky
M L
ML
Morrisett
J D
JD
D015119:Aminocaproic Acid / Q000494:pharmacology; D001054:Apolipoproteins A / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism*; D001120:Arginine / Q000494:pharmacology; D002850:Chromatography, Gel; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015228:Hypertriglyceridemia / Q000378:metabolism; D015151:Immunoblotting; D017270:Lipoprotein(a) / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism*; D008239:Lysine / Q000494:pharmacology; D046911:Macromolecular Substances; D008970:Molecular Weight; D010956:Plasmapheresis; D011392:Proline / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D014148:Tranexamic Acid / Q000494:pharmacology; D014280:Triglycerides / Q000032:analysis / Q000378:metabolism*; D014461:Ultracentrifugation
D001054:Apolipoproteins A; D017270:Lipoprotein(a); D046911:Macromolecular Substances; D014280:Triglycerides; D014148:Tranexamic Acid; D001120:Arginine; D011392:Proline; D008239:Lysine; D015119:Aminocaproic Acid