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CLINICAL STUDIES

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

^a Department of Cardiology, Benjamin Franklin Hospital, Free University Berlin, Berlin, Germany

Manuscript received June 21, 1999; revised manuscript received December 30, 1999, accepted February 21, 2000.

Reprint requests and correspondence: Dr. A. Dörner, University Hospital Benjamin Franklin, Free University of Berlin, Department of Cardiology, Hindenburgdamm 30, 12200 Berlin, Germany
doerner{at}ukbf.fu-berlin.de

OBJECTIVES

This study evaluates the relevance of an enteroviral infection and the intramyocardial T-cell immune response for the alteration in the adenine nucleotide translocator isoform transcription pattern (ANTitp) in patients 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 myocardium 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 immunohistochemistry.

RESULTS

The ANTitp was found to be altered in 21 csIHD patients. Enteroviral 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 infiltration with CD3⁺, CD45R0⁺ and CD8⁺ T-cells was substantially lower in myocardial specimens with an altered ANTitp than in biopsies with a normal ANTitp. Combining the data, an altered ANTitp was primarily found in virus-positive heart tissue, which was less infiltrated with lymphocytes or not at all.

CONCLUSIONS

An enteroviral infection is linked to changes in the ANT isoform 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 human inflammatory heart disease.

Abbreviations and Acronyms   ANT = adenine nucleotide translocator   ANTitp = adenine nucleotide translocator isoform transcription pattern   CBV = Coxsackie B virus   csIHD = clinically suspected inflammatory heart disease   DCM = dilated cardiomyopathy   EF = ejection fraction   HPF = high power field   ICM = ischemic cardiomyopathy

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