POLYMORPHIC FORMS OF LP(A) WITH DIFFERENT STRUCTURAL AND FUNCTIONAL-PROPERTIES - COLD-INDUCED SELF-ASSOCIATION AND BINDING TO FIBRIN AND LYSINE-SEPHAROSE

Two different Lp(a) polymorphs were isolated from the same individual and shown to have important differences both in their solution propert ies and in interaction with lysine Sepharose and fibrin. One Lp(a) par ticle (d-Lp(a)) with a large apo(a) isoform had a density of 1.087 g/m l and a molecular weight of 3.17 million, while the other Lp(a) partic le with a small apo(a) isoform having a mobility faster than that of a poB was larger and had a molecular weight of 3.75 million and a densit y of 1.054 g/ml. D-Lp(a) underwent cold-induced self-association and a lso had a higher affinity for lysine Sepharose, whereas the other Lp(a ) polymorph did not. Both Lp(a) particles bound fibrin via two differe nt binding sites, one of which involved fibrin lysine residues which a re also recognized by plasminogen. Lysine-mediated binding of d-Lp(a) by fibrin was ten times stronger than that of the other Lp(a) particle , whereas non-lysine-mediated binding of either Lp(a) species by fibri n was of equal strength. At saturation, 80% of d-Lp(a) bound fibrin at sites that did not involve lysine residues, whereas only 33% of the o ther Lp(a) polymorph bound to these sites. These findings indicate tha t the binding of Lp(a) to fibrin is more complex than previously thoug ht and imposes another layer of difficulty on our understanding of how Lp(a) regulates and/or impairs fibrinolysis.