Mangin E L, Kugiyama K, Nguy J H, Kerns S A, Henry P D
Department of Medicine, Baylor College of Medicine, Houston, Tex 77030.
Circ Res. 1993 Jan;72(1):161-6. doi: 10.1161/01.res.72.1.161.
Exposure of isolated arteries to oxidatively modified low density lipoprotein (LDL) has been reported to suppress endothelium-dependent relaxation (EDR). To determine whether lipid degradation products in oxidized LDL contribute to impaired relaxation, we have tested the responsiveness of isolated rabbit aortas to endothelium-dependent relaxants (acetylcholine, ATP, and calcium ionophore A23187) and nitroglycerin before and after 2-hour incubations with selected lipids and LDL preparations. Concentrations (10 microM) of lecithin, phosphatidylserine, lysophosphatidylserine, sphingomyelin, phosphatidic acid, palmitate, arachidonate, and auto-oxidized arachidonate had no effect on EDR. Concentrations (10 microM) of lysolecithin, lyso-platelet activating factor, and sphingosine significantly suppressed endothelium-dependent relaxation. Native LDL (100 micrograms/ml incubation buffer) containing only small amounts of lysophosphatidylcholine exerted no effect on EDR. In contrast, LDL preparations oxidatively modified by exposure to cultured endothelial cells or copper inhibited EDR. When modified LDL was depleted of its lysolecithin by treatment with a selective phospholipase B (lysolecithinase), the inhibitory effects were attenuated. In contrast, native LDL accumulating lysolecithin under the influence of a phospholipase A2 (lecithinase) exerted inhibitory effects mimicking those of oxidized LDL. Lipids and lipoproteins had no effect on the responsiveness to nitroglycerin, an endothelium-independent vasodilator. We conclude that lysolecithin in oxidatively modified LDL contributes importantly to its vasomotor effects.
据报道，将分离的动脉暴露于氧化修饰的低密度脂蛋白（LDL）会抑制内皮依赖性舒张（EDR）。为了确定氧化LDL中的脂质降解产物是否导致舒张功能受损，我们在将分离的兔主动脉与选定的脂质和LDL制剂孵育2小时前后，测试了其对内皮依赖性舒张剂（乙酰胆碱、ATP和钙离子载体A23187）和硝酸甘油的反应性。卵磷脂、磷脂酰丝氨酸、溶血磷脂酰丝氨酸、鞘磷脂、磷脂酸、棕榈酸、花生四烯酸和自动氧化的花生四烯酸的浓度（10微摩尔）对EDR没有影响。溶血卵磷脂、溶血血小板活化因子和鞘氨醇的浓度（10微摩尔）显著抑制内皮依赖性舒张。仅含有少量溶血磷脂酰胆碱的天然LDL（100微克/毫升孵育缓冲液）对EDR没有影响。相反，通过暴露于培养的内皮细胞或铜而氧化修饰的LDL制剂抑制EDR。当用选择性磷脂酶B（溶血卵磷脂酶）处理使修饰的LDL耗尽其溶血卵磷脂时，抑制作用减弱。相反，在磷脂酶A2（卵磷脂酶）的影响下积累溶血卵磷脂的天然LDL发挥了类似于氧化LDL的抑制作用。脂质和脂蛋白对内皮非依赖性血管舒张剂硝酸甘油的反应性没有影响。我们得出结论，氧化修饰的LDL中的溶血卵磷脂对其血管舒缩作用有重要贡献。
