These data demonstrate that the detection of enterovirus RNA in the myocardium of patients with heart muscle disease at the time of initial investigation is associated with an adverse prognosis and that the presence of enterovirus RNA is an independent predictor of clinical outcome.
The aim of the investigation was to determine whether there are specific global quantitative and qualitative changes in protein expression in heart tissue from patients with dilated cardiomyopathy (DCM) compared with ischaemic heart disease and undiseased tissue. Two-dimensional (2-D) polyacrylamide gel electrophoresis and computer analysis was used to study protein alteration in DCM biopsy material (n=28) compared with donor heart biopsy samples (n=9) and explanted hearts from individuals suffering from ischaemic heart disease (IHD; n = 21). A total of 88 proteins displayed decreased abundance in DCM versus IHD material while five proteins had elevated levels in the DCM group (p<0.01). The most prominent changes occurred in the contractile protein myosin light chain 2 and in a group of proteins identified as desmin. These changes do not appear to be artefactual degradation events occurring during sample processing. These proteins are not apparent in electrophoretic separations of vascular tissue or cultured endothelial cells, mesothelial cells or cardiac fibroblasts, which are clearly distinguishable from the 2-D protein patterns of whole heart and of isolated cardiac myocytes and do not appear to reflect variations in the cellular composition of biopsy samples. The different protein patterns observed in cardiomyopathy showed no obvious relationship with New York Heart Association (NYHA) functional class or haemodynamic parameters. The study has demonstrated significant alterations in quantitative protein expression in the DCM heart which would have serious implications for myocyte function. These changes might be explained by altered protease activity in DCM which could exacerbate contractile dysfunction in the failing heart.
Enteroviruses are well recognized in the aetiology of myocarditis. Molecular hybridization using enterovirus group-specific probes shows that virus can be detected in endomyocardial biopsies and persists in myocardium after the inflammation heals. Virus persistence is associated with the subsequent development of dilated cardiomyopathy, progressing to end-stage disease requiring cardiac transplantation. Infectious virus cannot usually be isolated from myocardium nor can virus-specific antigens be detected after the initial inflammatory stage. Patients with healed myocarditis or dilated cardiomyopathy may have no histological evidence of inflammation despite detection of virus-specific RNA sequences by molecular hybridization. Persisting enterovirus RNA in dilated cardiomyopathy is the strongest known predictor of poor prognosis. The molecular mechanism of virus persistence is the selection of defective virus mutants during the initial phase of disease.
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