Adenine nucleotide translocator in dilated cardiomyopathy: pathophysiological alterations in expression and function.
Several findings pointed to an insufficient energy supply in heart muscle tissue of patients suffering from dilated cardiomyopathy (DCM). We found a lowered ANT transport capacity of the adenine nucleotide translocator (ANT), the only transport system for ATP and ADP in eucaryotic cells, in explanted hearts of DCM patients. The reduced ANT transport rate was accompanied by a marked elevation in total ANT protein caused by an increase in ANT 1 isoform protein. Simultaneously, a reduction in ANT 2 transcripts and an unchanged ANT 3 expression was observed. In contrast, patients with ischemic or valvular heart disease showed no alteration in ANT function or expression, which indicates the disease-specificity of these findings. With regard to autoimmunological and viral processes, which are thought to play an important role in the pathogenesis of DCM, we could show that the ANT function is reduced in the hearts of A.SW/Sn-J mice infected with the enterovirus Cox-sackie B3, and in those of guinea pigs immunized with purified myocardial ANT. Both treatments led to autoimmunological reactions against the ANT protein, that reduce the myocardial ANT transport capacity, thus disturbing energy metabolism and consequently depressing heart function. In contrast to these animal models, no restriction in ANT capacity was observed in hypoxic hearts of guinea pigs, which corresponds to the findings of unaffected ANT function in ischemic human hearts.
Dörner
A
A
Department of Cardiology, Benjamin Franklin Hospital, Free University of Berlin, Germany.
Schulze
K
K
Rauch
U
U
Schultheiss
H P
HP
D000818:Animals; D001692:Biological Transport; D002311:Cardiomyopathy, Dilated / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004734:Energy Metabolism; D006168:Guinea Pigs; D006801:Humans; D051379:Mice; D008929:Mitochondria, Heart / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism*
D000226:Mitochondrial ADP, ATP Translocases