Significance of the adenine nucleotide translocator in the pathogenesis of viral heart disease.
We found recently autoantibodies against the adenine nucleotide translocator (ANT), a carrier in the inner mitochondrial membrane, in sera of patients with myocarditis and dilated cardiomyopathy. To elucidate whether these antibodies are of pathophysiological importance, we investigated the function and expression of the adenine nucleotide translocator (ANT) in the heart muscle tissue of patients suffering from myocarditis and DCM. We found a markedly lowered transport capacity of the translocator accompanied by an elevation in total ANT protein content. The alteration in ANT protein amount is caused by an ANT isoform shift characterized by an increase in ANT 1 isoform protein associated with a decrease in ANT 2 isoform and an unchanged ANT 3 content. It could be shown that the isoform shift is not a progressive process during the disease period but an event in the early period of illness which becomes permanent. Simulating the effect of pathogenetic factors of autoimmunological diseases, we infected A/J mice with the enterovirus Coxsackie B3 and immunized guinea pigs with myocardial ANT protein. Both treatments led to autoimmunological responds and to a lowered myocardial transport capacity of ANT, to a disturbed energy metabolism and consequently to a depression of heart function.
Schultheiss
H P
HP
Benjamin Franklin Hospital, Free University, Berlin, Germany.
Schulze
K
K
Dörner
A
A
D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology; D002311:Cardiomyopathy, Dilated / Q000378:metabolism; D004268:DNA-Binding Proteins; D004770:Enterovirus; D029968:Escherichia coli Proteins; D006168:Guinea Pigs; D006331:Heart Diseases / Q000821:virology*; D006801:Humans; D051379:Mice; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism*; D009205:Myocarditis / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D014157:Transcription Factors / Q000276:immunology
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D014157:Transcription Factors; C074687:nhaR protein, E coli; D000226:Mitochondrial ADP, ATP Translocases