Group V sPLA2 hydrolysis of low-density lipoprotein results in spontaneous particle aggregation and promotes macrophage foam cell formation

Objectives-Secretory phospholipase A(2) (sPLA(2)) enzymes hydrolyze the sn-2 fatty acyl ester bond of phospholipids to produce a free fatty acid and a lysophospholid. Group V sPLA(2) is expressed in cultured macrophage cells and has high affinity for phosphatidyl choline-containing substrates. The present study assesses the presence of group V sPLA(2) in human and mouse atherosclerotic lesions and its activity toward low-density lipoprotein (LDL) particles. Methods and Results-Group V sPLA(2) was detected in human and mouse atherosclerotic lesions by immunohistochemical staining. Electron microscopic analysis showed that mouse group V sPLA(2)-modified LDL is significantly smaller (mean diameter+/-SEM=25.3+/-0.25 nm) than native LDL (mean diameter+/-SEM=27.7+/-0.29 nm). Hydrolysis by group V sPLA(2) induced spontaneous particle aggregation; the extent of aggregation was directly proportional to the degree of LDL hydrolysis. Group V sPLA(2) modification of LDL led to enhanced lipid accumulation in cultured mouse peritoneal macrophage cells. Conclusions-Group V sPLA(2) may play an important role in promoting atherosclerotic lesion development by modifying LDL particles in the arterial wall, thereby enhancing particle aggregation, retention, and macrophage uptake.