© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Disturbance of myocardial energy metabolism in experimental virus myocarditis by antibodies against the adenine nucleotide translocator
Department of Cardiology, Benjamin Franklin Hospital, Free University of Berlin, Berlin, Germany
* Corresponding address. Medizinische Klinik II, Kardiologie, Universitätsklinikum Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. Tel.: +49-30-8445-4162; fax: +49-30-8445-4141
Objective: The adenine nucleotide translocator (ANT) of the inner mitochondrial membrane is an autoantigen in myocarditis and in dilated cardiomyopathy. Clinical and experimental studies showed that specific autoantibodies inhibit the transmembrane nucleotide transport. In isolated hearts of guinea pigs immunized with the ANT, energy metabolism is disturbed. This metabolic disorder is related to functionally active specific antibodies and to a reduced heart function. This study tests whether similar immunological, metabolical and functional responses also occur in experimental virus myocarditis. Methods and results: Experimental virus myocarditis was induced in A.SW/SnJ-mice by Coxsackie B3 virus infection. Specific antibodies against the ANT were detected by Western Blot in 14 out of 19 infected animals. In the isolated perfused hearts of five of these 14 mice cytosolic and mitochondrial ATP/ADP-ratios, determined by nonaqueous fractionation, were significantly altered, signalling a reduced ANT function [cytosolic ATP/ADP: 59±18 vs. 136±20 (controls), mitochondrial ATP/ADP: 4.2±1.0 vs. 1.1±0.3], all P<0.05. Also, left ventricular pressure [43±9 vs. 78±6 mmHg (noninfected controls)], rate-pressure product (15.8±3.2 vs. 30.5±3.0 mmHg/min/1000), dp/dt (2410±222 vs. 3250±118 mmHg/s), and oxygen consumption (4.7±0.9 vs. 7.3±0.7 µmol/g/min), all P<0.05, were lowered. Conclusion: The data support the hypothesis that a virus infection alters cardiac energy metabolism and function by an antibody-mediated modulation of the function of the ANT.
KEYWORDS Myocarditis; Cardiomyopathy; Energy metabolism; Mitochondria; Hemodynamics
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  V. Temkin, Q. Huang, H. Liu, H. Osada, and R. M. Pope Inhibition of ADP/ATP Exchange in Receptor-Interacting Protein-Mediated Necrosis. Mol. Cell. Biol., March 1, 2006; 26(6): 2215 - 2225. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Fosslien Mitochondrial Medicine - Molecular Pathology of Defective Oxidative Phosphorylation Ann. Clin. Lab. Sci., January 1, 2001; 31(1): 25 - 67. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Dorner, M. Pauschinger, P. L. Schwimmbeck, U. Kuhl, and H.-P. Schultheiss The shift in the myocardial adenine nucleotide translocator isoform expression pattern is associated with an enteroviral infection in the absence of an active T-cell dependent immune response in human inflammatory heart disease J. Am. Coll. Cardiol., June 1, 2000; 35(7): 1778 - 1784. [Abstract] [Full Text] [PDF]
|
|