Schulze K, Schultheiss H P
Medizinische Klinik B, Heinrich-Heine Universität, Düsseldorf, Germany.
Eur Heart J. 1995 Dec;16 Suppl O:64-7. doi: 10.1093/eurheartj/16.suppl_o.64.
The ADP/ATP carrier is an autoantigen in myocarditis and dilated cardiomyopathy, both of which are diseases related to virus infections. Sera of these patients bear carrier-specific autoantibodies inhibiting transmembrane nucleotide transport on isolated mitochondria. To further assess the role of the ADP/ATP carrier in viral heart disease, guinea pigs were immunized with the isolated ADP/ATP carrier protein and A-strain mice were infected with coxsackie B3 virus. Both species generated specific and carrier-inactivating antibodies after immunization/infection. The transport activity of the ADP/ATP carrier-estimated from the cytosolic-mitochondrial difference of the phosphorylation potential of ATP (delta G[cyt-mit])-markedly declined in guinea pig and mice hearts. A close relationship was observed between the magnitude of reduction of delta G(cyt-mit) and the decrease of cardiac function. Therefore, it seems plausible that carrier dysfunction induced by viral infection creates an imbalance in myocardial energy metabolism, and is responsible for the impairment of cardiac function. The underlying mechanism might be an autoimmune reaction triggered via molecular mimicry or a modulation of the expression of ADP/ATP carrier isoforms changing the overall transport capacity of the cardiac ADP/ATP carrier.
ADP/ATP载体是心肌炎和扩张型心肌病中的一种自身抗原，这两种疾病均与病毒感染相关。这些患者的血清中含有载体特异性自身抗体，可抑制分离线粒体上的跨膜核苷酸转运。为了进一步评估ADP/ATP载体在病毒性心脏病中的作用，用分离的ADP/ATP载体蛋白对豚鼠进行免疫，并使A品系小鼠感染柯萨奇B3病毒。在免疫/感染后，这两个物种均产生了特异性且使载体失活的抗体。根据ATP磷酸化电位的胞质-线粒体差异（δG[cyt-mit]）估算的ADP/ATP载体转运活性，在豚鼠和小鼠心脏中显著下降。观察到δG（cyt-mit）降低的幅度与心功能下降之间存在密切关系。因此，病毒感染引起的载体功能障碍导致心肌能量代谢失衡，并导致心功能受损，这似乎是合理的。潜在机制可能是通过分子模拟引发的自身免疫反应，或ADP/ATP载体同工型表达的调节改变了心脏ADP/ATP载体的整体转运能力。
