Lipolysis of LDL by human secretory phospholipase A(2) induces particle fusion and enhances the retention of LDL to human aortic proteoglycans

The first morphological sign of atherogenesis is the accumulation of extrac ellular lipid droplets in the proteoglycan-rich subendothelial layer of the arterial intima. Secretory nonpancreatic phospholipase A(2) (snpPLA(2)), a n enzyme capable of lipolyzing LDL particles, is found in the arterial extr acellular matrix and in contact with the extracellular lipid droplets. We h ave recently shown that in the presence of heparin, lipolysis of LDL with b ee venom PLA(2) induces aggregation and fusion of the particles. Here, we s tudied the effect of human snpPLA(2) on the integrity of LDL particles and on their interaction with human aortic proteoglycans. In addition, the capa city of the proteoglycans to retain PLA(2)-lipolyzed LDL particles was test ed in a microtiter well assay. We found that lipolysis of LDL induced fusio n of proteoglycan-bound LDL particles, which increased their binding streng th to the proteoglycans, Moreover, lipolysis of LDL with snpPLA(2) under ph ysiological salt and albumin concentrations induced a 3-fold increase in th e amount of LDL bound to proteoglycans. The results imply a role for PLA, i n the retention and accumulation of LDL to the proteoglycan matrix in ather osclerosis.