INTERACTION OF LIPOPROTEIN (A) WITH THE EXTRACELLULAR-MATRIX

Differences in the interactions of lipoprotein(a) (Lp(a)) and low dens ity lipoprotein (LDL) with extracellular matrices may account for thei r different pathogenic effects and localization within atherosclerotic lesions. Accordingly, we have compared the binding of Lp(a), plasmino gen (which is highly homologous in structure to the apolipoprotein(a) [apo(a)] moiety of Lp(a)), and LDL with the extracellular matrix using Matrigel as a model. Under conditions where radiolabeled Lp(a) bound to the matrix, LDL binding was not observed. However, at higher LDL in put concentrations, binding of this lipoprotein was detected, suggesti ng a lower affinity interaction of LDL than Lp(a) with the matrix. Bin ding of Lp(a) and plasminogen was time dependent, specific, saturable and reversible, Lp(a) exhibited a higher affinity for Matrigel (K-d = 12-130 nM) than plasminogen (K-d = 0.86 mu M); but Lp(a) had fewer bin ding sites in the matrix than plasminogen. Both Lp(a) and plasminogen binding were inhibited by lysine analogs, implicating the lysine bindi ng sites associated with their kringle structures in the interactions. In addition, Lp(a) binding was inhibited by certain other amino acids , proline and alanine, and LDL. We conclude that the interaction of Lp (a) with the extracellular matrix involves multiple recognition specif icities that synergize to achieve a higher affinity interaction than o bserved for LDL and plasminogen. These differences may lead to differe nt pathogenetic mechanisms for these lipoprotein particles.