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Published on: January 12, 2015
Transcriptomal analysis of failing and nonfailing human hearts
M Steenman1, Y-W Chen, M Le Cunff
1Institut National de la Santé et de la Recherche Médicale U533, 44035 Nantes, France. marja.steenman@nantes.inserm.fr
Insights
This study analyzed gene expression in failing and nonfailing human hearts to understand heart failure. Key differences in gene profiles were found between healthy and diseased ventricles, offering insights into cardiac dysfunction.
Area of Science:
- Cardiovascular Biology
- Molecular Genetics
- Genomics
Background:
- Heart failure is a complex disease with diverse causes.
- Understanding normal and failing cardiac function at a molecular level is crucial.
Purpose of the Study:
- To compare gene expression profiles in failing and nonfailing human ventricles.
- To identify molecular differences in various heart failure conditions.
Main Methods:
- Large-scale gene expression analysis using oligonucleotide arrays (approx. 12,000 genes).
- Analysis of left ventricle (LV) and right ventricle (RV) samples from nonfailing, dilated cardiomyopathy (DCM), and ischemic cardiomyopathy (ICM) hearts.
- Stringent statistical analyses to identify differentially expressed genes.
Main Results:
- Identified 1,306 genes representing the general human cardiac expression profile.
- Found 95 differentially expressed genes between failing and nonfailing hearts, indicating dedifferentiation and apoptosis.
- Discovered 20 genes distinguishing failing LV from failing RV.
- No significant gene expression differences between DCM and ICM failing LVs were observed.
Conclusions:
- Gene expression analysis reveals transcriptomal landmarks for normal and failing cardiac function.
- Findings suggest a reversal to developmental gene expression and cardiomyocyte dedifferentiation in heart failure.
- Transcriptomal analysis of explanted hearts reflects end-stage failure rather than specific etiologies.
Abstract:
Heart failure is a multifactorial disease that may result from different initiating events. To contribute to an improved comprehension of normal cardiac function and the molecular events leading to heart failure, we performed large-scale gene expression analysis of failing and nonfailing human ventricle. Our aim was to define and compare expression profiles of 4 specific pathophysiological cardiac situations: 1) left ventricle (LV) from nonfailing heart; 2) LV from failing hearts affected by dilated cardiomyopathy (DCM); 3) LV from failing hearts affected by ischemic CM (ICM); 4) right ventricle (RV) from failing hearts affected by DCM or ICM. We used oligonucleotide arrays representing approximately 12,000 human genes. After stringent numerical analyses using several statistical tests, we identified 1,306 genes with a similar expression profile in all 4 cardiac situations, therefore representative of part of the human cardiac expression profile. A total of 95 genes displayed differential expression between failing and nonfailing heart samples, reflecting a reversal to developmental gene expression, dedifferentiation of failing cardiomyocytes, and involvement of apoptosis. Twenty genes were differentially expressed between failing LV and failing RV, identifying possible candidates for different functioning of both ventricles. Finally, no genes were found to be significantly differentially expressed between failing DCM and failing ICM LV, emphasizing that transcriptomal analysis of explanted hearts results mainly in identification of expression profiles of end-stage heart failure and less in determination of expression profiles of the underlying etiology. Taken together, our data resulted in identification of putative transcriptomal landmarks for normal and disturbed cardiac function.
