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

我们在95例血液透析患者中横断面研究了偶联因子6（CF 6）（一种内源性前列环素合成抑制剂）或不对称二甲基精氨酸（ADMA）（一种内源性一氧化氮合酶抑制剂）与心血管事件之间的相关性。血液透析患者血浆CF 6和ADMA水平比对照组高3倍，且两者呈正相关（r=0.25，p<0.05）。血浆CF 6与肌酐呈正相关（r=0.36，p<0.01），而血浆ADMA无相关性。合并缺血性心脏病（心肌梗死和/或心绞痛）的血液透析患者的CF 6和ADMA血浆浓度均高于无事件的患者。多元回归模型显示，CF 6（r=0.24，p=0.023）和ADMA（r=0.26，p=0.023）与血液透析患者缺血性心脏病的发生独立相关。总之，CF 6是终末期肾病患者缺血性心脏病的一个新的危险因素。该肽和ADMA的协同作用可能通过抑制前列环素和一氧化氮的产生而导致其发生，对照组的血浆CF 6水平为12.8±0.5 ng/ml（n=27 ; 15名男性和12名女性，平均年龄51岁），原发性高血压患者为17.6±1.7 ng/ml（n=30 ; 14名男性和16名女性，平均年龄50岁），终末期肾病患者中为33.2±0.9 ng/ml（n=95 ; 52名男性和43名女性，平均年龄58岁）。CF 6的心包液水平显著高于这些受试者的血浆水平（所有p<0.05），并且高于血浆的正常范围4-5倍。CF 6的产生在心脏中增强，并且CF 6可以以自电影或旁分泌方式发挥其作用。

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.