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

我们研究了氧化磷脂和溶血磷脂是否参与动脉粥样硬化的发病机制，得到以下结果：通过与大豆脂氧合酶或兔网织细胞15-脂氧合酶反应，鉴定了含有亚油基的PC衍生的血小板活化因子（PAF）样脂质，并采用气相色谱-质谱法对氧化后的PC进行了分析。检测两种paf样脂质（短链二羧酸半醛或含单羧酸的PC）；它们被认为是由PC氢过氧化物氧化碎裂产生的。含有二羧酸半醛残基的PC抑制脂多糖和干扰素-γ诱导的血管平滑肌细胞一氧化氮的产生。3 .金属离子依赖性溶血磷脂酶D在37℃条件下，在大鼠、人和兔的血浆或血清中水解溶血磷脂酰胆碱（LPC），生成具有生物活性的溶血磷脂酸（LPA）。在动物血浆和血清中发现溶血磷脂酶D比不饱和LPCs更能水解不饱和LPCs。血清溶血磷脂酶D活性在饲喂高胆固醇饲料1周时升高，在饲喂高胆固醇饲料2-3周时进一步升高，但在饲喂4周后下降到胆固醇负荷前的水平。此外，LPC和LPA水平随着胆固醇负荷的增加而逐渐升高。

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.