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Papers In Press, published online ahead of print December 1, 2004
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Department of Molecular Genetics, Maastricht University, Maastricht 6229ER
Corresponding Author: dewinther{at}gen.unimaas.nl
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 accumulation of modified lipoproteins in the vessel wall. Group IIa secretory phospholipase A2 (sPLA2 IIa) is a key candidate player in the enzymatic modification of low density lipoproteins. To study the role of sPLA2 IIa in macrophages during atherogenesis, transgenic mice were generated using the human sPLA2 IIa gene and the CD11b promoter. Bone marrow transplantations to LDLR deficient mice were performed to study sPLA2 IIa in atherosclerosis. After 10 weeks of high fat diet, mice overexpressing sPLA2 IIa in macrophages showed 2.3 fold larger lesions as compared to controls. Pathological examination revealed that sPLA2 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 sPLA2 IIa in macrophages. These data clearly show that macrophage sPLA2 IIa is a pro-atherogenic factor and suggests that the enzyme is regulating collagen production in the plaque and thus fibrotic cap development.
Revised on November 5, 2004
Accepted on November 21, 2004
Macrophage-specific overexpression of group IIa sPLA2 results in increased atherosclerotic lesion size and enhanced collagen deposition
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