The myocardial expression of the adenine nucleotide translocator isoforms is specifically altered in dilated cardiomyopathy.
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, but 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.
Dörner
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Medizinische Klinik II-Kardiologie und Pneumologie, Universitätsklinikum Benjamin Franklin, Freien Universität Berlin, Germany. doerner@ukbf.fu-berlin.de
Schultheiss
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HP
D001706:Biopsy; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006346:Heart Septum / Q000473:pathology; D006349:Heart Valve Diseases / Q000235:genetics / Q000473:pathology; D006352:Heart Ventricles / Q000473:pathology; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D000226:Mitochondrial ADP, ATP Translocases / Q000235:genetics*; D017202:Myocardial Ischemia / Q000235:genetics / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics
D007527:Isoenzymes; D012333:RNA, Messenger; D000226:Mitochondrial ADP, ATP Translocases