PXD015337

PXD015337 is an original dataset announced via ProteomeXchange.

Title	Therapeutic miR-132 inhibition reverses heart failure
Description	Despite 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.
HostingRepository	PRIDE
AnnounceDate	2020-01-09
AnnouncementXML	Submission_2020-01-09_10:51:42.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD015337
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Xiaoke Yin
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	Oxidation; Carbamidomethyl
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2019-09-06 01:00:58	ID requested
⏵ 1	2020-01-09 10:51:43	announced

Dataset with its publication pending

submitter keyword: Calcium Cycling/Excitation-Contraction Coupling, Contractile Function, Myocardial Biology, Translational Studies, Myocardial Infarction

Manuel Mayr
contact affiliation	Cardiovascular Division, King's College London, London, UK
contact email	manuel.mayr@kcl.ac.uk
lab head
Xiaoke Yin
contact affiliation	Cardiovascular Division, King's College London
contact email	xiaoke.yin@kcl.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD015337
     1. Label: PRIDE project
     2. Name: Therapeutic miR-132 inhibition reverses heart failure