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Series GSE140660 Query DataSets for GSE140660
Status Public on Nov 19, 2022
Title Hydrogel-based intramyocardial delivery of antimiR-195 after ischemia-reperfusion injury [UPyPEG_IR]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Background MicroRNAs are potent regulators of biology and disease. The miR-15 family  has been shown to regulate cardiomyocyte proliferation and antimiR-based inhibition induces a cardioprotective effect after myocardial infarction in mice. However, systemic delivery of antimiRs leads to accumulation in kidneys and liver, with relatively poor cardiac exposure. pH-responsive injectable hydrogels serve as a sustained-release drug delivery depot and could potentially be used to improve cardiac efficacy of antimiR therapeutics.

Objective Examine whether hydrogel can improve local delivery of antimiR-195 in ischemic hearts to increase cardiac efficacy and limit off-target effects.

Methods Study the effect of intramyocardial injections of hydrogel-formulated antimiR-195 under both baseline conditions and after ischemic injury.

Results Intracardiac injections of UPy-PEG induced a transient inflammatory response that was no longer present 7 days post-injection. In vitro experiments showed that antimiR-195 was released from the gel, and induced microRNA inhibition leading to downstream cardiomyocyte proliferation. In vivo, intramyocardial delivery of antimiR-195 in UPy-PEG enhanced cardiac target de-repression compared to PBS-dissolved antimiR-195, despite a low cardiac retention. After ischemic injury, this translated into a greater therapeutic effect by increasing both target de-repression and cardiomyocyte proliferation.

Conclusions UPy-PEG can be used as a cardiac delivery vehicle of antimiRs and intramyocardial injection of UPy-PEG formulated antimiR-195 is sufficient to improve cardiac efficacy of antimiR-195. Follow up experiments in large animals will enable us to assess the true added value of using UPy-PEG to increase cardiac exposure of antimiR therapies.
 
Overall design Healthy mice were subjected to cardiac ischemia-reperfusion injury (anesthesia, intubation, opening of thorax, ligation of LAD, reperfusion and intramyocardial injection (2x10µl) of Upy-PEG hydrogel; either with no drug or with antimiR-195. Hearts were harvested for RNA-analysis 3 days after injury injection.
There are 2 groups (Upy-PEG, UPy-PEG-antimiR) with 4 samples per group
 
Contributor(s) Eding JE, Vigil Garcia M, Vink M, Demkes CJ, Versteeg D, Kooijman L, Bakker MH, Schotman MJ, Dankers PY, van Rooij E
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Submission date Nov 19, 2019
Last update date Nov 21, 2022
Contact name Eva van Rooij
E-mail(s) e.vanrooij@hubrecht.eu
Organization name Hubrecht Institute
Lab Eva van Rooij
Street address Uppsalalaan 8
City Utrecht
ZIP/Postal code 3531KC
Country Netherlands
 
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (8)
GSM4176410 M54-LV-15
GSM4176411 M54-LV-17
GSM4176412 M54-LV-19
This SubSeries is part of SuperSeries:
GSE140661 Hydrogel-based intramyocardial delivery of antimiR-195
Relations
BioProject PRJNA590477
SRA SRP230620

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE140660_RAW.tar 1.1 Mb (http)(custom) TAR (of TXT)
GSE140660_counts_RPKM.txt.gz 977.9 Kb (ftp)(http) TXT
GSE140660_counts_raw.txt.gz 354.4 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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