Lipoprotein (a) is a substrate for factor XIIIa and tissue transglutaminase.

The mechanisms which mediate deposition of lipoprotein (a) (Lp(a)), an atherogenic lipoprotein particle, onto the vessel wall and cell surfaces are unknown. An irreversible deposition of Lp(a) may require the presence of enzymes that catalyze its binding to surface-oriented structures. Transglutaminases catalyze cross-linking of proteins as well as incorporation of primary amines into protein substrates. We studied whether tissue transglutaminase and/or activated Factor XIII (plasma derived or recombinant FXIIIa) incorporate primary amines into Lp(a). In the presence of Ca2+, Factor XIIIa and tissue transglutaminase catalyze incorporation of monodansylcadaverine or [14C]putrescine into purified Lp(a) in a specific and time-dependent manner. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that monodansylcadaverine became incorporated into the apo(a) portion of Lp(a). Lp(a) purified from five different donors showing different apo(a) phenotypes were substrates for tissue transglutaminases (TG). Western blot analysis confirmed that apo(a) was the major monodansylcadaverine carrying protein moiety of Lp(a). Tissue TG also extensively cross-linked the apo(a) portion of the Lp(a) particle. Characterization of the specificity of tissue TG showed that fibronectin, alpha 2-plasmin inhibitor, and apo(a) could be readily labeled with monodansylcadaverine by tissue TG, but other proteins including low density lipoprotein, IgG, alpha 1-proteinase inhibitor, and albumin showed poor or no reactivity. Direct comparison of Lp(a) with low density lipoprotein showed that apoB 100 was a poor substrate for transglutaminases. Recombinant apolipoprotein (a) proved to be an excellent substrate for TGs in that 1 mol of recombinant apolipoprotein (a) incorporated as much as 15 mol of [14C]putrescine, which corresponded to five times the amount of amine incorporated into Lp(a). The susceptibility of Lp(a) to transglutaminases suggests a mechanism whereby the interaction of Lp(a) with surface receptors and other surface oriented structures could be enzymatically altered.