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

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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.