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  • Title: Gene expression profiling from endomyocardial biopsy tissue allows distinction between subentities of dilated cardiomyopathy.
    Author: Ruppert V, Meyer T, Pankuweit S, Möller E, Funck RC, Grimm W, Maisch B, German Heart Failure Network.
    Journal: J Thorac Cardiovasc Surg; 2008 Aug; 136(2):360-369.e1. PubMed ID: 18692642.
    Abstract:
    OBJECTIVE: Expression profile analysis using endomyocardial biopsy specimens from patients with cardiomyopathies promises to improve the differential diagnosis of heart failure. METHODS: In this study, left ventricular endomyocardial biopsy specimens were obtained from 50 patients and histopathologically classified according to the World Heart Federation Task Force criteria as having dilated cardiomyopathy (n = 17), inflammatory cardiomyopathy (n = 11), myocarditis (n = 15), or pericarditis (n = 7). Microarrays were performed by hybridization of synthesized complementary DNA against a Lab-Arraytor60-combi microarray (SIRS-Lab, Jena, Switzerland). Differentially expressed genes were clustered hierarchically according to their variation in hybridization signals. RESULTS: In samples from patients with dilated cardiomyopathy, two different types of gene expression profiles were distinguishable. One pattern was unique for dilated cardiomyopathy and inflammatory cardiomyopathy, respectively, and the other more closely resembled that seen in samples from inflammatory heart disease. Additionally, we confirmed the microarray data by showing that dilated cardiomyopathy is associated with a reduced myocardial toll-like receptor 9 expression that resulted from progressive loss of functional cardiomyocytes. Taken together, our data demonstrate the utility and validity of microarrays from endomyocardial biopsy specimens in detecting subentities of dilated cardiomyopathy that do not differ histopathologically, but transcriptionally, from each other. The gene expression profile observed in one subgroup of patients with dilated cardiomyopathy is indicative of ongoing immune activation, albeit infiltrating immunocompetent cells were not detected histopathologically. CONCLUSION: Thus, our transcriptional data indicate that dilated cardiomyopathy constitutes a heterogeneous disease with an broad overlap to inflammatory heart disease.
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