PXD033501

PXD033501 is an original dataset announced via ProteomeXchange.

Title	Proteomic and phosphoproteomic profiling in heart failure with preserved ejection fraction (HFpEF)
Description	Although the prevalence of heart failure with preserved ejection fraction (HFpEF) is increasing, evidence-based therapies for HFpEF are rare, likely due to an incomplete understanding of this disease. This study sought to identify the cardiac-specific features of protein and phosphoprotein in a murine model of HFpEF using mass spectrometry. HFpEF mice developed moderate hypertension, left ventricle (LV) hypertrophy, lung congestion and diastolic dysfunction. Proteomics analysis of the LV tissue showed that 897 proteins were differentially expressed between HFpEF and Sham mice. We observed abundant changes in sarcomeric proteins, mitochondrial-related proteins, and NAD-dependent protein deacetylase sirtuin-3 (SIRT3). Upregulated pathways by GSEA analysis were related to immune modulation and muscle contraction, while downregulated pathways were predominantly related mitochondrial metabolism. Western blot analysis validated SIRT3 downregulated cardiac expression in HFpEF. Phosphoproteomics analysis showed that 72 phosphopeptides were differentially regulated between HFpEF and sham LV. Aberrant phosphorylation patterns mostly occurred in sarcomere proteins and nuclear-localized proteins associated with contractile dysfunction and cardiac hypertrophy. Seven aberrant phospho-sites were observed at the z disk binding region of titin. While total titin cardiac expression remained unaltered, its stiffer N2B isoform was significantly increased in HFpEF. Thus, these results show profound changes in proteins related to mitochondrial metabolism and function and the cardiac contractile apparatus in HFpEF. We propose that SIRT3 plays a key role and may be a target for drug development in HFpEF.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_07:31:35.650.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ryan Hekman
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-28 01:01:06	ID requested
1	2022-11-29 04:15:02	announced
⏵ 2	2023-11-14 07:31:37	announced	2023-11-14: Updated project metadata.

Valero-Mu, ñ, oz M, Saw EL, Hekman RM, Blum BC, Hourani Z, Granzier H, Emili A, Sam F, Proteomic and phosphoproteomic profiling in heart failure with preserved ejection fraction (HFpEF). Front Cardiovasc Med, 9():966968(2022) [pubmed]

submitter keyword: metabolism, proteomics, SIRT3, mitochondria,HFpEF, titin, phosphoproteomics

Flora Sam
contact affiliation	Boston University
contact email	florasam@bu.edu
lab head
Ryan Hekman
contact affiliation	Boston University
contact email	rhekman@bu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD033501
     1. Label: PRIDE project
     2. Name: Proteomic and phosphoproteomic profiling in heart failure with preserved ejection fraction (HFpEF)