Apolipoprotein(a) isoform size influences binding of lipoprotein(a) to plasmin-modified des-AA-fibrinogen

Lipoprotein(a) (Lp(a)) is a LDL-like particle with an additional glycoprotein, apo(a), linked to apolipoprotein B-100. Apo(a) is highly homologous to parts of the plasminogen molecule, and numerous investigations have shown interference of Lp(a) with functions of plasminogen. In this report we studied the influence of apo(a) phenotype on the binding of Lp(a) to plasmin-modified immobilized des-AA-fibrinogen (desafib-X). Results indicate that Lp(a) binds to desafib-X in a specific and saturable way. There was a strongly significant negative correlation between apo(a) isoform length and maximal number of Lp(a) particles bound to the desafib-X matrix (N=18, r=0.84, p=0.002). There was no relation between apo(a) isoform length and K d for the binding of Lp(a) to desaflb-X. In two donors (10%) no specific binding to desafib-X was observed, as well as to lysine-sepharose. In conclusion, apo(a) isoform length influences the amount of Lp(a) binding to desaflb-X. This implies that small isoforms apart from their usual higher plasma Lp(a) concentrations also are potentially more thrombogenic. The fact that Lp(a) from two donors did not bind to desafib-X, suggests that mutations may exist in the K4-10 domain of apo(a) abolishing its lysine-binding ability.