Platelet-activating factor (PAF)-like oxidized phospholipids: Relevance to atherosclerosis

Article type: Research Article

Authors: Akira Tokumura, | Tuneki Sumida, | Masaoki Toujima, | Kentaro Kogure, | Kenji Fukuzawa,

Affiliations: Faculty of Pharmaceutical Sciences, The University of Tokushima, Shomachi, Tokushima 770-8505, Japan

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Abstract: Lipid peroxidation is involved in the pathogenesis of chronic diseases including atherosclerosis. Oxidized lipoprotein has diverse biological activities and is believed to initiate atheroma formation and maturate fatty plaque. The active components of oxidized lipoproteins still remain to be clarified, but a likely candidate is the phosphatidylcholine (PC) having an {\it sn}-2-short-chain acyl group with a methyl, hydroxyl, aldehydic or carboxylic terminal. These unique PCs, formed by oxidative fragmentation of the polyunsaturated acyl group of the parent PC in liposomes, low density lipoproteins and blood plasma, induce platelet aggregation through the activation of the receptor for platelet-activating factor (PAF), due to their resemblance in structure with PAF. We have found that PAF-like lipids regulate DNA synthesis and production of nitric oxide independently of the activation of the PAF receptor in vascular smooth muscle cells. Regulation of vascular cell function through two distinct signaling pathways mediated by PAF-like lipids provides new insight into the mechanism of induction of atherosclerosis.

Keywords: platelet-activating factor, oxidized phosphatidylcholine, oxidized low density lipoprotein, atherosclerosis

Journal: BioFactors, vol. 13, no. 1-4, pp. 29-33, 2000