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| Status |
Public on Nov 03, 2014 |
| Title |
Genome-wide changes in gene expression during the development and after recovery from heart failure in a mouse model of transient cardiomyopathy. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Altered myocardial gene expression from heart failure (HF) has mostly been identified by single-point analysis of end-stage disease. This may miss earlier changes in gene expression that are transient and/or directionally opposite to those observed later. By sampling left ventricular myocardial tissue at different time points in a mouse model of cardiomyopathy, we examined differentially expressed transcripts between non-failing controls, early-HF (2 and 3 days after cardiac insult), peak-HF (10 days) and after recovery from HF (28 days). As a results, we found that gene expression followed varying patterns: Downregulation of metabolic pathways occurred early and was sustained into late stage-HF. In contrast, most signaling pathways undergo a complex biphasic pattern: Calcium signaling, p53, apoptosis and MAP-kinase pathways displayed a bi-directional response, declining early but rising late, while NF-κB-related transcription displayed the opposite pattern. The HF-induced transcriptomic changes were reversed after recovery at 28 days. We conclude that the myocardial transcriptome in evolving HF displays distinct and dynamic transcript clusters. Therapies targeting different phases of HF should consider these dynamic features when identifying high-value targets.
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| Overall design |
Mice expressing mutated estrogen receptor-coupled Cre under transcriptional control of cardiac-specific myosin heavy chain (MerCreMer, MCM, 005650;Jackson Laboratories, Bar Harbor, ME) were back-crossed for >10 generations with C57Bl6/J. Transient cardiomyopathy develops in these mice following 5 day exposure to tamoxifen free base (T5648, Sigma), with peak dysfunction at day 10 and full recovery after 4 weeks. Full transcriptome analyses were generated from flash-frozen left ventricular myocardium at different time points (control = baseline, day 2, day 3, day 10, and day 28).
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| Contributor(s) |
Barth AS, Rowell J, Kass DA |
| Citation(s) |
25159852 |
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| Submission date |
Feb 05, 2014 |
| Last update date |
Jun 14, 2018 |
| Contact name |
Andreas Sebastian Barth |
| E-mail(s) |
[email protected]
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| Phone |
+1 410 614 0032
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| Organization name |
Johns Hopkins University
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| Department |
Medicine, Division of Cardiology
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| Lab |
Tomaselli
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| Street address |
720 Rutland Ave.
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| City |
Baltimore |
| State/province |
MD |
| ZIP/Postal code |
21205 |
| Country |
USA |
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| Platforms (1) |
| GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
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| Samples (19)
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| Relations |
| BioProject |
PRJNA237353 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE54681_RAW.tar |
3.1 Mb |
(http)(custom) |
TAR |
| GSE54681_non-normalized.txt.gz |
2.0 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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