Schultheiss H P
Department of Cardiology, Heinrich-Heine University, Düsseldorf, Germany.
Circulation. 1993 May;87(5 Suppl):IV43-8.
After the identification and immunochemical characterization of the ADP/ATP carrier of the inner mitochondrial membrane as an organ- and a conformation-specific autoantigen in myocarditis and dilated cardiomyopathy, we investigated whether an immunoreaction against the ADP/ATP carrier leads to a disturbance of cellular energy metabolism and consequently of myocardial function.
Either immunization of guinea pigs with the isolated carrier protein or infection of A/J mice with coxsackievirus B3 induced heart reactive antibodies against the ADP/ATP carrier and led to a disturbance of the cellular energy metabolism: delta Gcyt-mit: 4.9 +/- 0.6 kJ/mol ATP (controls) to 2.3 +/- 1.1 kJ/mol ATP (immunized animals). In the isolated, perfused working heart preparation, the hemodynamic results of these hearts showed a > 50% reduction in external heart work. Because the amount of the decrease of external heart work and the magnitude of the reduction of delta Gcyt-mit showed a very close correlation, it must be suspected that the imbalance of the myocardial energy metabolism is responsible for the impairment of cardiac function.
These data suggest that virus infection of the myocardium as shown for viral myocarditis and dilated cardiomyopathy may lead to a disturbed function of the ADP/ATP carrier and, thus, may be the cause of impaired myocardial function.
在线粒体膜内膜的ADP/ATP载体被鉴定为心肌炎和扩张型心肌病中器官特异性和构象特异性自身抗原并进行免疫化学表征后，我们研究了针对ADP/ATP载体的免疫反应是否会导致细胞能量代谢紊乱，进而导致心肌功能紊乱。
用分离的载体蛋白免疫豚鼠或用柯萨奇病毒B3感染A/J小鼠，均可诱导产生针对ADP/ATP载体的心脏反应性抗体，并导致细胞能量代谢紊乱：细胞 - 线粒体间的ΔG：从4.9±0.6 kJ/mol ATP（对照组）降至2.3±1.1 kJ/mol ATP（免疫动物）。在离体灌注工作心脏标本中，这些心脏的血流动力学结果显示心脏外部做功减少超过50%。由于心脏外部做功减少量与细胞 - 线粒体间ΔG降低幅度显示出非常密切的相关性，因此必须怀疑心肌能量代谢失衡是心脏功能受损的原因。
这些数据表明，如病毒性心肌炎和扩张型心肌病所示的心肌病毒感染可能导致ADP/ATP载体功能紊乱，从而可能是心肌功能受损的原因。
