Effects of lysolecithin on the regulation of gene transcription in endothelial cells and plasma levels of secretary type II phospholipase A2 in coronary artery disease

溶血磷脂(LysoPC)广泛存在于动脉粥样硬化的动脉壁中，可改变多种内皮功能，诱导多种血管内皮细胞基因在动脉粥样硬化管壁和炎症部位表达。为了确定溶酶PC是否能调节内皮细胞中核因子-kB的活化，我们用溶酶C与培养的人脐静脉内皮细胞(HUVECs)孵育，并通过凝胶迁移率改变分析检测HUVECs核提取液中的核因子-kB结合活性。实验表明，溶血磷脂对血管内皮细胞核因子-kB活性的调节作用依赖于其浓度和孵育时间，内皮细胞蛋白激酶C(PKC)的激活可能部分参与了溶血磷脂诱导的核因子-kB的激活。动脉粥样硬化的动脉壁中至少有两种来源的溶血磷脂。其中一个来源是氧化型低密度脂蛋白(Ox-…更多的低密度脂蛋白)，积聚在动脉粥样硬化的动脉壁中。低密度脂蛋白的氧化与卵磷脂通过内在的低密度脂蛋白相关磷脂酶A2(PLA2)的作用而水解成溶血磷脂有关。因此，我们进一步研究了分泌型PLA2在动脉粥样硬化性冠状动脉疾病的病理生理学中的作用。外周循环PLA2放射免疫测定结果显示，劳力性心绞痛和陈旧性心肌梗死患者外周循环中主动脉根部、冠状静脉窦和股静脉血浆II型PLA2水平升高。急性心肌梗死患者外周血中PLA2水平升高，发病后3d达高峰，提示溶酶PC可通过调节动脉粥样硬化动脉中核因子-kB转录因子的激活来调节某些内皮基因的表达，PLA2可能在动脉粥样硬化性冠状动脉疾病的病理生理过程中起重要作用。较少

Lysolecithin (lysoPC), which abundantly exists in atherosclerotic arterial walls, has been shown to alter various endothelial functions and induce several endothelial genes expressed in atherosclerotic arterial walls and inflammatory sites. To determine whether lysoPC could modulate endothelial NF-kB activation, we incubated cultured human umbilical vein endothelial cells (HUVECs) with lysoPC and examined the NF-kB binding activity in the nuclear extracts of HUVECs by electrophoretic mobility shift assays. The experiments showed that lysoPC regulates endothelial NF-kB activity in a biphasic manner dependent on its concentration and incubation time, and the endothelial protein kinase C (PKC) activation may in part be involved in the lysoPC-induced NF-kB activation.Concentrations of lysolecithin are greatly increased in atherosclerotic arterial walls. There are at least two sources of lysolecithin found in atherosclerotic arterial walls. One souce is oxidized low-density lipoprotein (Ox- … More LDL), which accumulates in atherosclerotic arterial walls. LDL oxidation is associated with the hydrolysis of lecithin to lysoPC by the action of an intrinsic LDL-associated phospholipase A2 (PLA2). Thus, we further examined the role of secretary type II PLA2 in the pathophysiology of atherosclerotic coronary artery disease. The study with radioimmunoassay of PLA2 in peripheral circulation showed that plasma levels of type II PLA2 were increased in the peripheral circulation at aortic root, coronary sinus and femoral vein in effort angina and old myocardial infarction. The level of PLA2 was also increased in peripheral circulation in patients with acute myocardial infarction with a peak at 3th day after the onset of the disease.These results indicate that lysoPC could modulate expression of some endothelial genes through regulating the activation of transcription factor of NF-kB in atherosclerotic arteries and PLA2 may play an important role in the pathophysiology of atherosclerotic coronary artery disease. Less