on February 12, 2004
Published online before print February 12, 2004, doi: 10.1161/01.ATV.0000122363.02961.c1
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Submitted on January 7, 2004
Accepted on February 2, 2004
Group V sPLA2 Hydrolysis of Low-Density Lipoprotein Results in Spontaneous Particle Aggregation and Promotes Macrophage Foam Cell Formation
C. Ruth Wooton-Kee ;
From the Department of Internal Medicine, University of Kentucky Medical Center, Lexington, Kentucky.
* To whom correspondence should be addressed. 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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