Investigation on the involvment of oxidized phospholipids and lysophospholipids in the pathogenesis of atherosclerosis

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We examined whether oxidized phospholipids and lysophospholipids are involved in the pathogenesis of atherosclerosis, and obtained following results.1. We characterized platelet-activating factor (PAF)-like lipids derived from PC having a linoleoyl group on reaction with soybean lipoxygenase or rabbit reticulocyte 15-lipoxygenase, and analyzed the oxidized PC by gas chromatography-mass spectrometry. Two types of PAF-like lipids (short chain dicarboxylatesemialdehyde or monocarboxylate-containing PC) were detected ; they were suggested to be generated by oxidative fragmentation of PC hydroperoxides.2. PC containing a dicarboxylate semialdehyde residue inhibited the production of nitric oxide induced by lipopolysaccharide and interferon-γ in vascular smooth muscle cells.3. Metal ion-dependent lysophospholipase D hydrolyzed lysophosphatidylcholine (LPC) to bioactive lysophosphatidic acid (LPA) in rat, human and rabbit plasma or serum during incubation at 37℃.4. Lysophospholipase D in animal plasma and serum was found to hydrolyze unsaturated LPCs over unsaturated LPCs.5. Serum lysophospholipase D activity was increased at I week after feeding a high-holesterol diet, followed by further increase at 2-3 weeks, but after 4 weeks, the activity was declined to the level before cholesterol-loading. In addition, the levels of LPC and LPA were gradually increased with the cholesterol-loading for 12 weeks.