title: Lipolysis of LDL by human secretory phospholipase A(2) induces particle fusion and enhances the retention of LDL to human aortic proteoglycans.
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 A(2) (snpPLA(2)), 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 PLA(2) induces aggregation and fusion of the particles. Here, we studied the effect of human snpPLA(2) on the integrity of LDL particles and on their interaction with human aortic proteoglycans. In addition, the capacity of the proteoglycans to retain PLA(2)-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 snpPLA(2) 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 PLA(2) in the retention and accumulation of LDL to the proteoglycan matrix in atherosclerosis.
authors.affiliation: Wihuri Research Institute, Helsinki, Finland.
authors.forename: J K
authors.initials: JK
authors.lastname: Hakala
authors.forename: K
authors.initials: K
authors.lastname: Oörni
authors.forename: M O
authors.initials: MO
authors.lastname: Pentikäinen
authors.forename: E
authors.initials: E
authors.lastname: Hurt-Camejo
authors.forename: P T
authors.initials: PT
authors.lastname: Kovanen
mesh_terms: D001011:Aorta / Q000378:metabolism*; D001161:Arteriosclerosis / Q000378:metabolism; D054501:Group II Phospholipases A2; D006801:Humans; D008066:Lipolysis; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008561:Membrane Fusion; D010741:Phospholipases A / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism*
chemical_list: D008077:Lipoproteins, LDL; D011509:Proteoglycans; D010741:Phospholipases A; D054501:Group II Phospholipases A2