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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:762.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Group V sPLA₂ Hydrolysis of Low-Density Lipoprotein Results in Spontaneous Particle Aggregation and Promotes Macrophage Foam Cell Formation

C. Ruth Wooton-Kee; Boris B. Boyanovsky; Munira S. Nasser; Willem J.S. de Villiers; Nancy R. Webb

From the Department of Internal Medicine, University of Kentucky Medical Center, Lexington, Kentucky.

Correspondence to Dr N. R. Webb, Department of Internal Medicine, University of Kentucky Medical Center MN520, 800 Rose Street, Lexington, KY 40536-0084. E-mail nrwebb1{at}uky.edu

Objectives— 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.

Methods and Results— 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.

Conclusions— 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.

Key Words: atherosclerosis • group V secretory phospholipase A₂ • LDL aggregation • macrophages

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