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ERX10627624: GDF15 antagonism limits severe heart failure and prevents cardiac cachexia in mice
1 ILLUMINA (Illumina NovaSeq 6000) run: 12.9M spots, 1.3G bases, 389.2Mb downloads

Design: GDF15 antagonism limits severe heart failure and prevents cardiac cachexia in mice
Submitted by: EBI (European Bioinformatics Institute)
Study: GDF15 antagonism limits severe heart failure and prevents cardiac cachexia in mice
show Abstracthide Abstract
Heart failure and associated cachexia is an unresolved and important problem. We report a new model of severe heart failure that consistently results in cachexia. Mice lacking the integrated stress response (ISR) induced eIF2a phosphatase, PPP1R15A, exhibit a dilated cardiomyopathy and severe weight loss following irradiation, whilst wildtype mice are unaffected. This is associated with increased expression of Gdf15 in the heart and increased levels of GDF15 in the circulation. We provide evidence that blockade of GDF15 activity prevents cachexia and slows the progression of heart failure. Our data suggests that cardiac stress mediates a GDF15 dependent pathway that drives weight loss and worsens cardiac function. We show relevance of GDF15 to lean mass and protein intake with patients with heart failure. Blockade of GDF15 could constitute a novel therapeutic option to limit cardiac cachexia and improve clinical outcomes in patients with severe systolic heart failure.
Sample: Sample 3
SAMEA112868712 • ERS14875367 • All experiments • All runs
Organism: Mus musculus
Library:
Name: Sample 3_p
Instrument: Illumina NovaSeq 6000
Strategy: RNA-Seq
Source: TRANSCRIPTOMIC
Selection: RANDOM
Layout: PAIRED
Construction protocol: The fresh hearts were harvested and snap frozen in liquid nitrogen.Meanwhile for 7. mice, tissues were harvested and immediately snap frozen in liquid nitrogen and stored at _80_C until further analysis. Animals were perfused with cold PBS to remove any trace of blood. Aortas were harvested and cleaned of contaminated tissues under a dissection microscope mouse 6-8 weeks Pppr15a-/- with irradiation Align to GRCm39 reference genome using star (version 2.6.1d) RNA was then extracted (and in some instances treated with DNase1 on-column) using the RNeasy isolation kit following the manufacturer’s instructions. For RNA isolation, approximately 30-50 mg of tissue was placed in Lysing Matrix D tubes and homogenized in 800 ml Triazol (Qiazol,QIAGEN) using the Fastprep-24 Homogenizer for 30 s at 4-6 m/s (MP Biomedical), or a rotor-stator homogenizer. The resultant supernatant was transferred to an RNase free tube and 200 ml chloroform (Sigma) added. The samples were vortexed and centrifuged at 13 000 rpm for 15 min at 4_C. The upper phase was then transferred to a RNase free tube and mixed with equal volume of 70% ethanol before loading onto RNA isolation spin columns (QIAGEN).
Experiment attributes:
Experimental Factor: time: 0
Experimental Factor: genotype: wild type genotype
Runs: 1 run, 12.9M spots, 1.3G bases, 389.2Mb
Run# of Spots# of BasesSizePublished
ERR1119632212,892,2421.3G389.2Mb2024-08-01

ID:
34520829

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