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

基本信息

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

项目摘要

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.

我们对 95 名血液透析患者的 CF6 和 ADMA 血浆水平进行了横断面调查，其中耦合因子 6 (CF6)（前列环素合成的内源性抑制剂）或不对称二甲基精氨酸 (ADMA)（一氧化氮合酶的内源性抑制剂）与心血管事件之间的关联。血液透析患者中的含量比对照个体高 3 倍，并且这两种化合物之间存在正相关性（r=0.25， CF6 的血浆浓度与肌酐呈正相关（r=0.36，p<0.01），而合并缺血性心脏病的血液透析患者的血浆 ADMA 浓度则较高。（心肌梗塞和/或心绞痛）与未发生事件的患者相比，在多元回归模型中，CF6 的血浆浓度。（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。综上所述，CF6是血液透析患者缺血性心脏病的新危险因素。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（n=27；15 名男性和 12 名女性，平均年龄 51 岁）CF6 为 12.8±0.5 ng/ml，原发性高血压患者（n=30；14 名男性和 16 名女性）CF6 为 17.6±1.7 ng/ml平均年龄 50 岁的女性），终末期肾病患者为 33.2±0.9 ng/ml（n=95； 52 名男性和 43 名女性，平均年龄为 58 岁），心包液中 CF6 水平显着高于这些受试者的血浆水平（全部 p<0.05），并且比正常范围高出 4-5 倍。心脏中 CF6 的生成增强，并且 CF6 可能以自分泌或旁分泌的方式发挥其作用。