Endothelin Converting Enzyme and Endothelin in Cardiovascular Diseases

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。

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.