Quantitative trait locus mapping in mice identifies phospholipase Pla2g12a as novel atherosclerosis modifier.

BACKGROUND AND AIMS:) background. It was the aim of the current study to identify causative genes at this locus. METHODS: background, to validate the Chr3 locus. Candidate genes were identified using genome-wide expression analyses. Differentially expressed genes were validated using quantitative PCRs in F0 and F2 mice and their functions were investigated in pathophysiologically relevant cells. RESULTS: congenic mice, which developed 2.5 greater atherosclerotic lesions compared to littermate controls (p=0.039). Pla2g12a was highly expressed in aortic endothelial cells in vivo, and knocking-down Pla2g12a expression by in cultured vascular endothelial cells or macrophages increased their adhesion to ECs in vitro. CONCLUSIONS:Our data establish Pla2g12a as an atheroprotective candidate gene in mice, where high expression levels in ECs and macrophages may limit the recruitment and accumulation of these cells in nascent atherosclerotic lesions.

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