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| Status |
Public on Jul 02, 2014 |
| Title |
Comparative RNA-sequencing analysis of myocardial and circulating small RNAs in human heart failure and their utility as biomarkers [small RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Heart failure is associated with high morbidity and mortality and its incidence increases worldwide. MicroRNAs (miRNAs) are potential markers and targets for diagnostic and therapeutic applications, respectively. We determined myocardial and circulating miRNA abundance and its changes in patients with stable and end-stage heart failure before and at different time points after mechanical unloading by a left ventricular assist device (LVAD) by small-RNA-sequencing. MiRNA changes in failing heart tissues partially resembled that of fetal myocardium. Consistent with prototypical miRNA–target-mRNA interactions, target mRNA levels were negatively correlated to changes in abundance for highly expressed miRNAs in heart failure and fetal hearts. The circulating small RNA profile was dominated by miRNAs, and fragments of tRNAs and small cytoplasmic RNAs. Heart- and muscle-specific circulating miRNAs (myomirs) increased up to 140-fold in advanced heart failure, which coincided with a similar increase in cardiac troponin I protein, the established marker for heart injury. These extracellular changes nearly completely reversed 3 months following initiation of LVAD support. In stable heart failure, circulating miRNAs showed less than 5-fold differences compared to normal, and myomir and cardiac troponin I levels were only captured near the detection limit. These findings provide the underpinning for miRNA-based therapies and emphasize the usefulness of circulating miRNAs as biomarkers for heart injury performing similar to established diagnostic protein biomarkers.
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| Overall design |
Total RNA isolated from human left ventricular myocardium of failing hearts due to dilated or ischemic cardiomyopathy before and after mechanical unloading by a left ventricular assist device, and fetal myocardium compared to non-failing postnatal myocardium was subjected to multiplexed small RNA-sequencing on the Illumina platform. mRNA gene expression data using Illumina HumanHT-12v4 beadarrays for a subset of the myocardial samples is available (GSE52601).
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| Contributor(s) |
Akat KM, Tuschl T, Schulze PC |
| Citation(s) |
25012294 |
| Submission date |
Dec 06, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Kemal Marc Akat |
| E-mail(s) |
kakat@rockefeller.edu
|
| Phone |
212-327-7645
|
| Organization name |
The Rockefeller University
|
| Lab |
Laboratory of RNA Molecular Biology, Thomas Tuschl
|
| Street address |
1230 York Avenue
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (2) |
| GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (185)
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| This SubSeries is part of SuperSeries: |
| GSE53081 |
Comparative RNA-sequencing analysis of myocardial and circulating small RNAs in human heart failure and their utility as biomarkers |
|
| Relations |
| BioProject |
PRJNA230811 |
| SRA |
SRP033566 |
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