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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

溶血卵磷脂对冠心病内皮细胞基因转录及血浆分泌型II型磷脂酶A2水平的影响

基本信息

批准号：
07670793
负责人：
KUGIYAMA Kiyotaka
金额：
$ 1.54万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670793/
关键词：
Atherosclerosis Lysolecithin Endothelial Cells Protein Kinase C Gene Transcription Phospholipase A2 phospholipase A_2

项目摘要

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

溶血磷脂酶（lysoprotein，lysoPC）大量存在于动脉粥样硬化的血管壁中，能改变多种内皮功能，并诱导多种内皮基因在动脉粥样硬化的血管壁和炎症部位表达。为了确定lysoPC是否可以调节内皮NF-kB的激活，我们培养的人脐静脉内皮细胞（HUVECs）与lysoPC和检测的NF-kB结合活性的细胞核提取物的HUVECs的电泳迁移率变动分析。实验表明，lysoPC对内皮细胞NF-κ B活性的调节呈双相性，其作用依赖于其浓度和孵育时间，并且内皮细胞蛋白激酶C（PKC）的激活可能部分参与了lysoPC诱导的NF-κ B活性的激活。在动脉粥样硬化的动脉壁中发现至少有两种溶血素来源。一种来源是氧化低密度脂蛋白（Ox-LDL）。 ...更多信息 LDL），其积聚在动脉粥样硬化的动脉壁中。LDL氧化与内在LDL相关磷脂酶A2（PLA 2）作用下卵磷脂水解为lysoPC有关。因此，我们进一步研究了II型PLA 2在动脉粥样硬化性冠状动脉疾病病理生理学中的作用。外周循环中PLA_2的放射免疫测定结果表明，劳力型心绞痛和陈旧性心肌梗塞患者主动脉根部、冠状静脉窦和股静脉血浆中Ⅱ型PLA_2水平升高。急性心肌梗死患者外周血中PLA 2水平也明显升高，发病后第3天达高峰，提示lysoPC可通过调节NF-κ B转录因子的活化来调节动脉粥样硬化血管内皮相关基因的表达，PLA 2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。少