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PXD015337-1

PXD015337 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTherapeutic miR-132 inhibition reverses heart failure
DescriptionDespite some success of pharmacotherapies targeting primarily neurohormonal dysregulation, heart failure is a growing global pandemic with increasing burden. Treatments that improve the disease by reversing heart failure at the cardiomyocyte level are lacking. MicroRNAs (miRNA) are transcriptional regulators of gene expression, acting through complex biological networks, and playing thereby essential roles in disease progression. Adverse structural remodelling of the left ventricle due to myocardial infarction (MI) is a common pathological feature leading to heart failure. We previously demonstrated increased cardiomyocyte expression of the miR-212/132 family during pathological cardiac conditions. Transgenic mice overexpressing the miR-212/132 cluster (miR-212/132-TG) develop pathological cardiac remodelling and die prematurely from progressive HF. Using both knockout and antisense strategies, we have shown miR-132 to be both necessary and sufficient to drive the pathological growth of cardiomyocytes in a murine model of left ventricular pressure overload. Based on the findings, we proposed that miR-132 may serve as a therapeutic target in heart failure therapy. Here we provide novel mechanistic insight and translational evidence for the therapeutic efficacy in small and large animal models (n=135) of heart failure. We demonstrate strong PK/PD relationship, dose-dependent efficacy and high clinical potential of a novel optimized synthetic locked nucleic acid phosphorothioate backbone antisense oligonucleotide inhibitor of miR-132 (antimiR-132) as a next-generation heart failure therapeutic.
HostingRepositoryPRIDE
AnnounceDate2020-01-09
AnnouncementXMLSubmission_2020-01-09_10:51:42.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD015337
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterXiaoke Yin
SpeciesList scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationListOxidation; Carbamidomethyl
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-09-06 01:00:58ID requested
12020-01-09 10:51:43announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Calcium Cycling/Excitation-Contraction Coupling, Contractile Function, Myocardial Biology, Translational Studies, Myocardial Infarction
Contact List
Manuel Mayr
contact affiliationCardiovascular Division, King's College London, London, UK
contact emailmanuel.mayr@kcl.ac.uk
lab head
Xiaoke Yin
contact affiliationCardiovascular Division, King's College London
contact emailxiaoke.yin@kcl.ac.uk
dataset submitter
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Dataset FTP location
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