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

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

Abstract

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 sPLA 2 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 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.

Original languageEnglish
Pages (from-to)762-767
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume24
Issue number4
DOIs
StatePublished - Apr 2004

Keywords

  • Atherosclerosis
  • Group V secretory phospholipase A
  • LDL aggregation
  • Macrophages

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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