Isolation, quantitation, and characterization of a stable complex formed by Lp[a] binding to triglyceride-rich lipoproteins. |
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Authors: | J W Gaubatz R C Hoogeveen A S Hoffman K G Ghazzaly H J Pownall J Guevara M L Koschinsky J D Morrisett |
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Institution: | Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. |
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Abstract: | Lipoprotein a] (Lpa]) is a cholesterol-rich lipoprotein resembling LDL to which a large polymorphic glycoprotein, apolipoprotein a] (apoa]), is covalently coupled. Lpa] 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 Lpa] present in five HTG subjects was found in the triglyceride-rich lipoprotein (TRL) fraction. The Lpa]-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 Lpa], 70-88% was in the form of a lipoprotein resembling conventional Lpa]. Incubation of Lpa]-depleted TRL with native Lpa] resulted in a reconstituted Lpa]-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 Lpa] to TRL. We observed the preferential binding of Lpa] containing higher apparent molecular weight apoa] polymorphs to TRL both in native and reconstituted Lpa]-TRL complexes. A disproportionate amount of Lpa] was bound to the larger TRL particles. Although most apoa] bound to TRL was in the form of conventional Lpa] particles, lipid-free recombinant apoa] was observed to bind TRL.These results provide unequivocal evidence of the existence of an Lpa]-TRL complex under pathophysiologic conditions. The metabolic fate of the Lpa]-TRL complex, which is more abundant in hypertriglyceridemia, may be different from that of conventional Lpa], and may contribute uniquely to the progression or severity of cardiovascular disease. |
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