© 2001 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Lipolysis of LDL by Human Secretory Phospholipase A2 Induces Particle Fusion and Enhances the Retention of LDL to Human Aortic Proteoglycans
From the Wihuri Research Institute, Helsinki, Finland (J.K.H., K.Ö., M.O.P., P.T.K.), and Wallenberg Laboratory for Cardiovascular Research, Department of Heart and Lung Disease, Göteborg University, Sahlgrenska University Hospital, Gothenburg, and AstraZeneca, R&D, Cell Biology and Biochemistry, Mölndal, Sweden (E.H.-C.).
Correspondence to Katariina Öörni, Wihuri Research Institute, Kalliolinnantie 4, FIN-00140 Helsinki, Finland. E-mail kati.oorni{at}wri.fi
Abstract—The first morphological sign of atherogenesis is the accumulation of extracellular lipid droplets in the proteoglycan-rich subendothelial layer of the arterial intima. Secretory nonpancreatic phospholipase A2 (snpPLA2), an enzyme capable of lipolyzing LDL particles, is found in the arterial extracellular matrix and in contact with the extracellular lipid droplets. We have recently shown that in the presence of heparin, lipolysis of LDL with bee venom PLA2 induces aggregation and fusion of the particles. Here, we studied the effect of human snpPLA2 on the integrity of LDL particles and on their interaction with human aortic proteoglycans. In addition, the capacity of the proteoglycans to retain PLA2-lipolyzed LDL particles was tested in a microtiter well assay. We found that lipolysis of LDL induced fusion of proteoglycan-bound LDL particles, which increased their binding strength to the proteoglycans. Moreover, lipolysis of LDL with snpPLA2 under physiological salt and albumin concentrations induced a 3-fold increase in the amount of LDL bound to proteoglycans. The results imply a role for PLA2 in the retention and accumulation of LDL to the proteoglycan matrix in atherosclerosis.
Key Words: phospholipases • LDL • fusion • retention • proteoglycans
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