ADENINE-NUCLEOTIDE TRANSLOCATOR IN DILATED CARDIOMYOPATHY - PATHOPHYSIOLOGICAL ALTERATIONS IN EXPRESSION AND FUNCTION

Several findings pointed to an insufficient energy supply in heart mus cle tissue of patients suffering from dilated cardiomyopathy (DCM). We found a lowered ANT transport capacity of the adenine nucleotide tran slocator (ANT), the only transport system for ATP and ADP in eucaryoti c cells, in explanted hearts of DCM patients. The reduced ANT transpor t rate was accompanied by a marked elevation in total ANT protein caus ed by an increase in ANT 1 isoform protein. Simultaneously, a reductio n 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 disea se-specificity of these findings. With regard to autoimmunological and viral processes, which are thought to play an important role in the p athogenesis of DCM, we could show that the ANT function is reduced in the hearts of A.SW/Sn-J mice infected with the enterovirus Coxsackie B 3, and in those of guinea pigs immunized with purified myocardial ANT. Both treatments led to autoimmunological reactions against the ANT pr otein, that reduce the myocardial ANT transport capacity, thus disturb ing energy metabolism and consequently depressing heart function. In c ontrast to these animal models, no restriction in ANT capacity was obs erved in hypoxic hearts of guinea pigs, which corresponds to the findi ngs of unaffected ANT function in ischemic human hearts.