Phospholipase A2 type-II binds to extracellular matrix biglycan -: Modulation of its activity on LDL by colocalization in glycosaminoglycan matrixes

We recently reported the presence of secretory, nonpancreatic phospholipase A(2) type II (snpPLA(2); EC 3.1.1.4) in human atherosclerotic arteries (Hurt-Camejo et al, Arterioscler Thromb Vase Biol. 1997;17:300-309). SnpPLA(2) may generate the proinflammatory products lysophospholipids and free fatty acids, thus contributing to atherogenesis when acting on low density lipoproteins (LDLs) retained in the arterial wall. Immunohistochemical studies showed that smooth muscle cells (SMCs) in human arterial tissue are the main sources of snpPLA(2). In cultures of human arterial SMCs, snpPLA(2) interacts with versican and smaller heparan/chondroitin sulfate proteoglycans (PGs) secreted as soluble components into the medium. In the present study, we investigated the binding of snpPLA(2) to extracellular matrix (ECM) PGs produced by SMCs. The results show that snpPLA(2) can bind to the ECM at physiological salt concentrations. ECM-bound snpPLA(2) was active, hydrolyzing phosphatidylcholine-containing micelles. Soluble chondroitin-6-sulfate at concentrations >1 mu mol/L, but not heparin or heparan sulfate, was able to release ECM-bound snpPLA(2). The PG mainly involved in the binding of snpPLA(2) was identified as biglycan. Perlecan was also present in the ECM synthesized by SMCs, but it contributed less to the binding of snpPLA(2). Experiments with immobilized glycosaminoglycans indicated that snpPLA(2) hydrolyzed 7-fold more LDL phospholipids when the lipoprotein and the enzyme were colocalized in a matrix with chondroitin-6-sulfate compared with one with heparin. These data suggest that retention of snpPLA(2) in ECMs of different composition may modulate the enzymatic activity of snpPLA(2) toward LDL. The results presented in this work support the hypothesis of the potential contribution of snpPLA(2) to atherosclerosis.