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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1998;18:1934-1941.)
© 1998 American Heart Association, Inc.

Original Contributions

Phospholipase A₂ Type II Binds to Extracellular Matrix Biglycan

Modulation of Its Activity on LDL by Colocalization in Glycosaminoglycan Matrixes

Peter Sartipy; Göran Bondjers; Eva Hurt-Camejo

From the Wallenberg Laboratory for Cardiovascular Research, Department of Heart and Lung Disease, Göteborg University, Gothenburg, Sweden.

Correspondence to Peter Sartipy, Wallenberg Laboratory, Sahlgrenska University Hospital, S-413 45 Gothenburg, Sweden. E-mail Peter.Sartipy{at}wlab.wall.gu.se

Abstract—We recently reported the presence of secretory, nonpancreatic phospholipase A₂ type II (snpPLA₂; EC 3.1.1.4) in human atherosclerotic arteries (Hurt-Camejo et al, Arterioscler Thromb Vasc Biol. 1997;17:300–309). SnpPLA₂ 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 snpPLA₂. In cultures of human arterial SMCs, snpPLA₂ 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 snpPLA₂ to extracellular matrix (ECM) PGs produced by SMCs. The results show that snpPLA₂ can bind to the ECM at physiological salt concentrations. ECM-bound snpPLA₂ was active, hydrolyzing phosphatidylcholine-containing micelles. Soluble chondroitin-6-sulfate at concentrations >1 µmol/L, but not heparin or heparan sulfate, was able to release ECM-bound snpPLA₂. The PG mainly involved in the binding of snpPLA₂ was identified as biglycan. Perlecan was also present in the ECM synthesized by SMCs, but it contributed less to the binding of snpPLA₂. Experiments with immobilized glycosaminoglycans indicated that snpPLA₂ 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 snpPLA₂ in ECMs of different composition may modulate the enzymatic activity of snpPLA₂ toward LDL. The results presented in this work support the hypothesis of the potential contribution of snpPLA₂ to atherosclerosis.

Key Words: phospholipase A₂ type II • proteoglycans • vascular cells • LDL • atherosclerosis

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