The myocardial expression of the adenine nucleotide translocator isoforms is specifically altered in dilated cardiomyopathy
The myocardial expression of the adenine nucleotide translocator isoforms is specifically altered in dilated cardiomyopathy
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DOI：
10.1007/s000590050004
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发表时间：
2000-05-01
期刊：
影响因子：
1.7
通讯作者：
Schultheiss, HP
中科院分区：
文献类型：
--
作者：
Dörner, R;Schultheiss, HP
腺嘌呤核苷酸转位子（adenine nucleotide translocator， ANT）是ADP和ATP的唯一线粒体载体，结合了线粒体能量产生和细胞质能量消耗过程。在扩张型心肌病（DCM）患者的外植心脏组织中，观察到ANT功能受损。为了阐明是否改变的ANT异构体组成可能是限制ANT功能的原因，我们分析了扩张型心肌病患者心肌中ANT异构体的表达模式。应用聚合酶链反应技术对29例扩张型心肌病（n = 29）、22例缺血性心肌病（n = 22）和7例瓣膜性心肌病（n = 7）移植心脏的ANT异构体mRNA谱进行分析。选取12例无心脏病患者的心肌作为对照。此外，我们还对47例扩张型心肌病患者进行了右心室活检。在扩张型心肌病患者的心脏组织中发现了ANT同种异构体转录谱的变化，但在缺血性或瓣膜性心肌病患者的心脏组织中没有发现。这种变化的特征是ANT1 mRNA百分比增加，ANT2 mRNA百分比减少，ANT3 mRNA比例不变。脑室和隔膜均受移位影响。在持续扩张型心肌病患者的心内膜标本中也发现了这种改变。发现扩张型心肌病特有的ANT亚型改变。它不是终末期心力衰竭的普遍现象，而是在心脏最终受损之前就已经发生了。因此，改变的ANT异构体表达似乎是心肌病特异性基因程序扩张的一个特征。
The adenine nucleotide translocator (ANT), the only mitochondrial carrier for ADP and ATP, combines mitochondrial energy-producing and cytosolic energy-consuming processes The ANT function was observed to be impaired in explanted heart tissue from patients with dilated cardiomyopathy (DCM). In order to clarify whether an altered ANT isoform composition might be responsible for the restricted ANT function, we analyzed the ANT isoform expression pattern in the myocardium of patients suffering from dilated cardiomyopathy.The ANT isoform mRNA pattern was analyzed in explanted hearts from patients with dilated cardiomyopathy (n = 29), ischemic (n = 22) and valvular cardiomyopathy (n = 7) using the polymerase chain reaction technique. Myocardium from 12 subjects without heart disease was used as control. In addition, right ventricular biopsies from 47 patients with dilated cardiomyopathy who underwent cardiac catheterization were tested.A shift in the ANT isoform transcription profile was found in heart tissue from patients with dilated cardiomyopathy, but not in those from patients with ischemic or valvular cardiomyopathy. The shift was characterized by an increase in the ANT1 mRNA percentage, a decrease in ANT2 and an unchanged ANT3 proportion. Both ventricles and the septum were affected by the shift. The alteration was also found in endomyocardial specimens taken from patients with ongoing dilated cardiomyopathy.An alteration in the ANT isoform pattern was found to be specific for dilated cardiomyopathy. It is not a general phenomenon of end-stage heart failure, bur occurs already before the heart is finally damaged. Therefore, an altered ANT isoform expression appears to be a feature of a dilated cardiomyopathy-specific gene program.