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Group V sPLA 2 Hydrolysis of Low-Density Lipoprotein Results in Spontaneous Particle Aggregation and Promotes Macrophage Foam Cell Formation

2004; Lippincott Williams & Wilkins; Volume: 24; Issue: 4 Linguagem: Inglês

10.1161/01.atv.0000122363.02961.c1

1524-4636

Clavia Ruth Wooton‐Kee, Boris B. Boyanovsky, Munira Nasser, Willem J.S. de Villiers, Nancy R. Webb,

Diabetes, Cardiovascular Risks, and Lipoproteins

Secretory phospholipase A2 (sPLA2) enzymes hydrolyze the sn-2 fatty acyl ester bond of phospholipids to produce a free fatty acid and a lysophospholid. Group V sPLA2 is expressed in cultured macrophage cells and has high affinity for phosphatidyl choline-containing substrates. The present study assesses the presence of group V sPLA2 in human and mouse atherosclerotic lesions and its activity toward low-density lipoprotein (LDL) particles.Group V sPLA2 was detected in human and mouse atherosclerotic lesions by immunohistochemical staining. Electron microscopic analysis showed that mouse group V sPLA2-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 sPLA2 induced spontaneous particle aggregation; the extent of aggregation was directly proportional to the degree of LDL hydrolysis. Group V sPLA2 modification of LDL led to enhanced lipid accumulation in cultured mouse peritoneal macrophage cells.Group V sPLA2 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.