PXD048363

PXD048363 is an original dataset announced via ProteomeXchange.

Title	Targeting HDAC6 to treat heart failure with preserved ejection fraction, Mouse heart LC-MS with PTMscan
Description	Heart failure with preserved ejection fraction (HFpEF) poses therapeutic challenges due to the limited treatment options. Building upon our previous research that demonstrates the efficacy of histone deacetylase 6 (HDAC6) inhibition in a genetic cardiomyopathy model, we investigate HDAC6’s role in HFpEF due to their shared mechanisms of inflammation and metabolism. Here, we show that inhibiting HDAC6 with TYA-018 effectively reverses established heart failure and its associated symptoms in HFpEF mouse models. Additionally, in mice lacking the Hdac6 gene, HFpEF progression is delayed and they are resistant to TYA-018’s effects. The efficacy of TYA-018 is comparable to a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and their combination shows enhanced effects. Mechanistically, TYA-018 restores gene expression related to hypertrophy, fibrosis, and mitochondrial energy production in HFpEF heart tissues. Furthermore, TYA-018 also inhibits activation of human cardiac fibroblasts and enhances mitochondrial respiratory capacity in cardiomyocytes. In this work, our findings show that HDAC6 impacts heart pathophysiology and is a promising target for HFpEF treatment.
HostingRepository	PRIDE
AnnounceDate	2024-01-17
AnnouncementXML	Submission_2024-01-17_13:10:05.414.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Farshad Farshidfar
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-09 13:48:46	ID requested
⏵ 1	2024-01-17 13:10:05	announced

Dataset with its publication pending

submitter keyword: Mouse, PTMscan, LC-MS, Heart, acetylated residue

Farshad Farshidfar
contact affiliation	CVG group, Tenaya Therapeutics Inc., South San Francisco, CA United States
contact email	ffarshidfar@tenayathera.com
lab head
Farshad Farshidfar
contact affiliation	Tenaya Therapeutics
contact email	farshidfar@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD048363
     1. Label: PRIDE project
     2. Name: Targeting HDAC6 to treat heart failure with preserved ejection fraction, Mouse heart LC-MS with PTMscan