Macrophage-specific overexpression of group IIa sPLA2 increases atherosclerosis and enhances collagen deposition

S.A.I. Ghesquiere, M.J.J. Gijbels, M. Anthonsen, P.J.J. van Gorp, I. van der Made, B. Johansen, M.H. Hofker, M.P.J. de Winther

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Abstract

Macrophage-specific overexpression of group IIa sPLA2 increases atherosclerosis and enhances collagen deposition.

Ghesquiere SA, Gijbels MJ, Anthonsen M, van Gorp PJ, van der Made I, Johansen B, Hofker MH, de Winther MP.

Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.

Atherosclerosis is a chronic inflammatory disease of the vessel wall characterized by the accumulation of lipid-laden macrophages and fibrotic material. The initiation of the disease is accompanied by the accumulation of modified lipoproteins in the vessel wall. Group IIa secretory phospholipase A(2) (sPLA(2) IIa) is a key candidate player in the enzymatic modification of low density lipoproteins. To study the role of sPLA(2) IIa in macrophages during atherogenesis, transgenic mice were generated using the human sPLA(2) IIa gene and the CD11b promoter. Bone marrow transplantation to LDL receptor-deficient mice was performed to study sPLA(2) IIa in atherosclerosis. After 10 weeks of high-fat diet, mice overexpressing sPLA(2) IIa in macrophages showed 2.3-fold larger lesions compared with control mice. Pathological examination revealed that sPLA(2) IIa-expressing mice had increased collagen in their lesions, independent of lesion size. However, smooth muscle cells or fibroblasts in the lesions were not affected. Other parameters studied, including T-cells and cell turnover, were not significantly affected by overexpression of sPLA(2) IIa in macrophages. These data clearly show that macrophage sPLA(2) IIa is a proatherogenic factor and suggest that the enzyme regulates collagen production in the plaque and thus fibrotic cap development.
Original languageEnglish
Pages (from-to)201-210
Number of pages9
JournalJournal of Lipid Research
Volume46
Issue number2
DOIs
Publication statusPublished - 1 Jan 2005

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