Phospholipase A₂ Modification Enhances Lipoprotein(a) Binding to the Subendothelial Matrix

Summary

Lipoprotein(a), Lp(a), is found in the extracellular matrix in athero-sclerotic plaques, but with a different localization than LDL. A two-compartment system, with a monolayer of endothelial cells forming a barrier, was used to compare the transport, cell binding, and retention of Lp(a) and LDL into the subendothelial matrix. Baseline values for transport and retention of Lp(a) and LDL were not significantly different. Incubation with lipoprotein lipase or sphingomyelinase caused modest and similar increases in transport and retention of the two lipo-proteins. In contrast, incubation with phospholipase A₂ (PLA₂) resulted in a marked (4-fold) increase in retention of Lp(a) on the subendothelial matrix, but a lesser (2-fold) increase in LDL retention. Moreover, PLA₂ treatment of Lp(a) enhanced its binding to individual matrix proteins (fibronectin, laminin, or collagen) by 4-10 times above that of LDL. The enzymatic activity of PLA₂ was responsible for its effect on Lp(a) binding. The lysine binding sites of Lp(a) contributed to the increased binding of PLA₂-modified Lp(a) to the matrix, and the enhanced lysine binding functions of PLA₂-modified Lp(a) was demonstrated by two independent approaches. Thus, PLA₂ modification leads to enhanced interactions of lipoproteins with the extracellular matrix, and this effect is more pronounced with Lp(a).

• References

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