Endothelin Converting Enzyme and Endothelin in Cardiovascular Diseases

内皮素转换酶和内皮素在心血管疾病中的作用

• 批准号: 12670685
• 负责人: KOHNO masakazu
• 金额: $ 2.11万
• 依托单位: Kagawa Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670685/
• 关键词: endothelin; endothelin converting enzyme; statin; EPA; HGF; basic FGF; angiotensin II; atherosclerosis; 動脈硬化症; 遺伝子治療; 高血圧; 臓器障害

A vasoconstrictive and growth-promoting peptide, endothelin-1, is found to play a role in the initiation and development of atherogenesis. The objectives of the present study were to determine whether statin, eicosapentaenoic acid (EPA) can affect endothelin-1 production and also determine whether hepatocyte growth factor (HGF) and basic fibroblast growth factor (FGF) can affect endothelin-1 production. Media concentrations of endothelin-1 were measured by a radioimmunoassay using the polyclonal antibody for synthetic endothelin-1. Fetal calf serum (FCS) and angiotensin II stimulated endothelin-1 production in a concentration-dependent manner in these cells. Statin and EPA inhibited endothelin-1 production. On the other hand, HGF did not affect endothlin-1 production significantly. HGF also did not affect endothelin-1 production. These results suggest that statin and EPA exert antiatherosclerotic effect through inhibiting endothelin-1 production and that HGF, but not basic FGF, did not affect endothelin-1 production of cultured rat vascular SMCs, and the HGF may be more advantageous for clinical application than basic FGF.

内皮素-1是一种血管收缩和生长促进肽，被发现在动脉粥样硬化的发生和发展中起作用。本研究的目的是确定他汀类药物，二十碳五烯酸（EPA）是否可以影响内皮素-1的生产，并确定肝细胞生长因子（HGF）和碱性成纤维细胞生长因子（FGF）是否可以影响内皮素-1的生产。使用合成内皮素-1的多克隆抗体通过放射免疫测定法测量内皮素-1的培养基浓度。胎牛血清（FCS）和血管紧张素II刺激内皮素-1的生产在这些细胞中的浓度依赖性的方式。他汀和EPA抑制内皮素-1的产生。另一方面，HGF对内皮素-1的产生没有显著影响。HGF也不影响内皮素-1的产生。提示他汀类药物和EPA通过抑制内皮素-1的产生而发挥抗动脉粥样硬化的作用; HGF对培养的大鼠血管平滑肌细胞内皮素-1的产生无影响，而碱性FGF对内皮素-1的产生无影响，提示HGF可能比碱性FGF更有利于临床应用。

项目成果

Kohno M, Ohmori K, Wada Y, et al.: "Inhibition by elcosapentaeoic acid of oxidized LDL - and lysophosphatidylcholine-induced human coronary artery smooth muscle cell production of endothelin"J. Vasc. Res.. 38 (4). 379-388 (2001)

Kohno M、Ohmori K、Wada Y 等人：“二十碳五烯酸对氧化 LDL 和溶血磷脂酰胆碱诱导的人冠状动脉平滑肌细胞内皮素生成的抑制”J。

Kohno M, Yasunari K, Maeda K, et al.: "Effects of cardiac natriuretic peptides on oxidized low-density lipoprotein- and lysophosphatidylcholine-induced human mesangial cell migration"Hypertension. 35 (4). 971-977 (2000)

Kohno M、Yasunari K、Maeda K 等人：“强心钠肽对氧化低密度脂蛋白和溶血磷脂酰胆碱诱导的人系膜细胞迁移的影响”高血压。

Masakazu Kohno: "Effects of cardiac natriuretic peptides on oxidized low-density lipoprotein-and lysophosphatidylcholine-induced human mesangial cell migration"Hypertension. 35. 971-977 (2000)

Masakazu Kohno：“强心钠肽对氧化低密度脂蛋白和溶血磷脂酰胆碱诱导的人系膜细胞迁移的影响”高血压。

河野雅和: "Nitric oxide合成阻害ラットの血中エンドセリンレベルならびに標的臓器障害の進展に及ぼすテモカプリルの効果"Progress in Medicine. 20. 849-853 (2000)

Masakazu Kono：“替莫普利对一氧化氮合成抑制大鼠血液内皮素水平和靶器官损伤发展的影响”医学进展 20. 849-853 (2000)。

Kohno Masakazu et al: "Suppression by Eicosapentaenoic Acid of Oxidized Low-Density Lipoprotein and Lysophosphatidylcholine-Induced Migration in Cultrued Rat Vascular Smooth Muscle Cells"Metabolism. 49. 560-562 (2000)

Kohno Masakazu 等人：“二十碳五烯酸对氧化低密度脂蛋白和溶血磷脂酰胆碱诱导的培养大鼠血管平滑肌细胞迁移的抑制”代谢。