A study on the role of coupling factor 6 in the pathogenesis of heart disease

耦合因子6在心脏病发病机制中的作用研究

• 批准号: 15590714
• 负责人: OSANAI Tomohiro
• 金额: $ 2.24万
• 依托单位: Hirosaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590714/
• 关键词: coupling factor 6; prostacyclin; mitochondria; myocardial infarction; valvular heart disease; end-stage renal disease; Mitochondria; Vasoconstrictor; Coupling factor 6; Ischemic heart disease; End-stage renal disease; Prostacyclin; Hypertensio; coupling factor 6; prostacyclin; mitochondria; myocardial infarction; valvular heart disease; end-stage renal disease; Mitochondria; Vasoconstrictor; Coupling factor 6; Ischemic heart disease; End-stage renal disease; Prostacyclin; Hypertensio

We investigated cross-sectionally the association between coupling factor 6 (CF6), an endogenous inhibitor of prostacyclin synthesis, or asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase and cardiovascular events in 95 hemodialysis patients. Plasma levels of CF6 and ADMA were 3-fold higher in hemodialysis patients than in control individuals, and there was a positive correlation between these two compounds (r=0.25, p<0.05). Plasma concentration of CF6 was positively correlated with that of creatinine (r=0.36, p<0.01), whereas plasma level of ADMA was not. Plasma concentrations of CF6 and ADMA were both higher in hemodialysis patients complicating ischemic heart disease (myocardial infarction and/or angina) than in those free of events. In a multiple regression model, plasma concentration of CF6 (r=0.24, p=0.023) and that of ADMA (r=0.26, p=0.023) were independently related to the occurrence of ischemic heart disease in hemodialysis patients. In conclusion, CF6 is a novel risk factor for ischemic heart disease in end-stage renal disease. Synergism of this peptide and ADMA might contribute to its occurrence presumably by inhibition of prostacyclin and nitric oxide production.The plasma levels of CF6 were 12.8±0.5 ng/ml in control subjects (n=27 ; 15 men and 12 women with a mean age of 51 years), 17.6±1.7 ng/ml in patients with essential hypertension (n=30 ; 14 men and 16 women with a mean age of 50 years), and 33.2±0.9 ng/ml in patients with end-stage renal disease (n=95 ; 52 men and 43 women with a mean age of 58 years). The pericardial fluid level of CF6 was significantly higher than the plasma levels of these subjects (all p<0.05), and was 4-5 fold elevated above the normal range of the plasma. The generation of CF6 is enhanced in the heart and CF6 may exert its effect in an autocine or paracrine fashion.

我们在横截面上研究了耦合因子6（CF6）（CF6），一种前列环蛋白合成的内源性抑制剂，或不对称的二甲基精氨酸（ADMA），这是95个血液溶液患者中一氧化氮合酶和心血管事件的内源性抑制剂。血液透析患者的血浆CF6和ADMA水平比对照个体高3倍，并且这两种化合物之间存在正相关（r = 0.25，p <0.05）。 CF6的血浆浓度与肌酐的等离子浓度呈正相关（r = 0.36，p <0.01），而adma的血浆水平与肌酐浓度无关。在血液透析患者中​​，CF6和ADMA的血浆浓度均高于缺血性心脏病（心肌梗死和/或心绞痛）的复杂性。在多元回归模型中，CF6的血浆浓度（r = 0.24，p = 0.023）和ADMA的血浆浓度（r = 0.26，p = 0.023）与血液透析患者中​​缺血性心脏病的发生独立相关。总之，CF6是末期肾脏疾病中缺血性心脏病的新型危险因素。这种胡椒和ADMA的协同作用可能会导致其发生，大概是通过抑制前列环蛋白和一氧化氮的产生。对照组受试者的血浆CF6水平为12.8±0.5 ng/ml（n = 27; 15名男性和12名女性，平均年龄为51岁）为17.6±1.7 ng/ml，患有原发性高血压患者（n = 30; 14名男性和16名男性和16名男性和16岁的男性，平均50岁），以及33.2±0.9 ng/ml = 93 ng/ml = 43 ng/ml = n3 ng/ml = 52 ng/ml。平均年龄58岁的妇女）。 CF6的心包流体水平明显高于这些受试者的血浆水平（所有P <0.05），并且在血浆正常范围以上升高了4-5倍。 CF6的产生在心脏中得到增强，CF6可能会以汽车或旁分泌方式执行其效果。