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

OBJECTIVES This study evaluates the relevance of an enteroviral infection a nd the intramyocardial T-cell immune response for the alteration in the ade nine nucleotide translocator isoform transcription pattern (ANTitp) in pati ents suspected of having myocardial inflammation. BACKGROUND The ANT, the only mitochondrial carrier for ADP and ATP, plays a significant role in the energy metabolism and is involved in the apoptosis process. Its function and expression were found to be altered in the myoca rdium of patients with dilated cardiomyopathy and myocarditis. Methods The ANTitp was analyzed in endomyocardial biopsies from 53 patients with clinically suspected inflammatory heart disease (csIHD). Enteroviral RNA was detected in the biopsies using the reverse transcripted polymerase chain reaction technique. The activation of the cellular immune system was assessed by the quantification of T-lymphocytes employing immunohistochemis try. RESULTS The ANTitp was found to be altered in 21 csIHD patients. Enterovira l genome was found in the heart of 71.4% of these patients, but only 37.5% of the patients with a normal ANTitp were virus-positive (p < 0.02). The in filtration with CD3(+), CD45R0(+) and CD8(+) T-cells was substantially lowe r in myocardial specimens with an altered ANTitp than in biopsies with a no rmal ANTitp. Combining the data, an altered ANTitp was primarily found in v irus-positive heart tissue, which was less infiltrated with lymphocytes or not at all. CONCLUSIONS An enteroviral infection is linked to changes in the ANT isofor m expression in human heart tissue, which shows little or no evidence of an active T-cell dependent immune response. These results make a contribution to a better understanding of the pathophysiology of enterovirus-induced hu man inflammatory heart disease. (J Am Coll Cardiol 2000;35: 1778- 84) (C) 2 000 by the American College of Cardiology.