Phospholipase A2 modification enhances lipoprotein(a) binding to the subendothelial matrix.
Lipoprotein(a), Lp(a), is found in the extracellular matrix in atherosclerotic 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 lipoproteins. 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).
Hoover-Plow
J
J
Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, The Cleveland Clinic Foundation, Ohio 44195, USA.
Khaitan
A
A
Fless
G M
GM
D000818:Animals; D002417:Cattle; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D017270:Lipoprotein(a) / Q000378:metabolism*; D010741:Phospholipases A / Q000494:pharmacology*; D054467:Phospholipases A2; D011485:Protein Binding / Q000187:drug effects; D051381:Rats
D016326:Extracellular Matrix Proteins; D017270:Lipoprotein(a); D010741:Phospholipases A; D054467:Phospholipases A2