ASSOCIATION OF ADENOVIRUS INFECTION WITH APOPTOSIS IN THE PATHOGENESIS OF MYOCARDITIS AND DILATED CARDIOMYOPATHY • 97

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It has recently been reported that apoptosis is a potential pathogenetic mechanism of idiopathic dilated cardiomyopathy (IDCM). Using polymerase chain reaction (PCR) of nucleic acid extracted from myocardial samples, we have accumulated considerable evidence linking chronic adenovirus infection of the myocardium with pediatric IDCM and myocarditis. Several of the early region proteins of adenovirus, notably E1A and the E1B proteins, have been implicated in the control of apoptosis.

Methods: We used the TUNEL staining technique to detect apoptotic nuclei in cardiac sections and to determine whether there is a link between adenovirus infection and apoptosis. Cardiac sections from 3 groups of patients were stained. The experimental group comprised sections from 6 patients with myocarditis/IDCM in which adenovirus infection was demonstrated by PCR. The first control group consisted of samples from 5 patients with myocarditis/IDCM but were adenovirus negative, while the second consisted of samples from 5 patients with either congenital heart disease or hypertrophic cardiomyopathy, also adenovirus negative. As positive controls, cardiac sections from a patient with myocardial infarction and sections from Burkitt's lymphoma were used.

Results: In the 2 control groups there was either no, or occasional, positively stained nuclei (less than 5 per section). In contrast, in each of the sections from the experimental group focal areas of stained nuclei were detected, particularly myocytes and endothelial cells. In samples from myocarditis patients, some infiltrating lymphocytes were also positive. In such areas, stained nuclei represented up to 1% of the total nuclei, and between 0.01 and 0.1% of the nuclei in the entire section.

Conclusions: These data suggest that adenovirus infection may play an etiologic role in myocarditis and IDCM by inducing apoptosis in the infected myocyte or endothelial cell. We are currently investigating the patterns of expression of the E1A and E1B regions in such samples by immunohistochemistry and reverse-transcription PCR.

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