Objective-We previously have shown that lysophosphatidylcholine (lysoPC) regulates proteoglycan synthesis by vascular smooth muscle cells (SMCs). Given the accumulating evidence for reactive oxygen species (ROS) as mediators of a variety of effects of lysoPC, the present study evaluates the potential role of ROS as intermediate molecules in the regulation of proteoglycan synthesis by lysoPC. Methods and Results-LysoPC (10 mol/L) was found to stimulate rapid and sustained generation of ROS by

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... , as indicated using a fluorescent probe for measuring intracellular oxidants and fluorescence-activated cell sorting. This was not associated with cytotoxicity, as evaluated by fluorescence microscopy using MitoTracker Red or propidium iodide, cell number, cell protein, or lactate dehydrogenase release. Pretreatment with catalase or superoxide dismutase, specific scavengers of hydrogen peroxide and superoxide, respectively, blocked the ability of lysoPC to stimulate both accumulation of ROS and proteoglycan synthesis. Most importantly, these enzymatic antioxidants prevented lysoPC from stimulating the synthesis of proteoglycans with enhanced lipoprotein-binding properties, as quantified by a gel shift binding assay. Conclusions-These findings strongly suggest that ROS are key mediators in the ability of lysoPC to regulate proteoglycan synthesis and that these effects can be inhibited by antioxidants. (Arterioscler Thromb Vasc Biol. 2006;26:494-500.)