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Myocardial transcriptome analysis of human arrhythmogenic right ventricular cardiomyopathy (ARVC).
MedLine Citation:
PMID:  22085907     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy primarily of the right ventricle characterized through fibrofatty replacement of cardiomyocytes. The genetic etiology in ARVC patients is most commonly caused by dominant inheritance and high genetic heterogeneity. Though histological examinations of ARVC affected human myocardium reveals fibrolipomatous replacement, the molecular mechanisms leading to loss of cardiomyocytes are largely unknown.We therefore analyzed the transcriptomes of 6 ARVC hearts and compared our findings to 6 non-failing donor hearts (NF). In order to characterize the ARVC-specific transcriptome, we compared our findings to samples from 7 patients with idiopathic dilated cardiomyopathy (DCM). The myocardial DCM and ARVC samples were prepared from hearts explanted during an orthotropic heart transplantation representing myocardium from endstage heart failure patients (NYHA IV). From each heart, left (LV) and right ventricular (RV) myocardial samples were analyzed by Affymetrix HG-U133 Plus 2.0 arrays, adding up to six sample groups. Unsupervised cluster analyses of the groups revealed a clear separation of NF and cardiomyopathy samples. However, in contrast to the other samples, the analyses revealed no distinct expression pattern in LV and RV of myocardial ARVC samples. We further identified differentially expressed transcripts using t-tests and found transcripts separating diseased and NF ventricular myocardium. Of note, in failing myocardium only about 15-16% of the genes are commonly regulated compared to NF samples. In addition both cardiomyopathies are clearly distinct on the transcriptome level. Comparison of the expression patterns between the failing RV and LV using a paired t-test revealed a lack of major differences between LV and RV gene expression in ARVC hearts. Our study is the first analysis of specific ARVC-related RV and LV gene expression patterns in terminal failing human hearts.
Authors:
Anna Gärtner; Patrick Schwientek; Peter Ellinghaus; Holger Summer; Stefan Golz; Astrid Kassner; Uwe Schulz; Jan Gummert; Hendrik Milting
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-15
Journal Detail:
Title:  Physiological genomics     Volume:  -     ISSN:  1531-2267     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9815683     Medline TA:  Physiol Genomics     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Herz- und Diabeteszentrum NRW.
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